Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-120180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-420180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-820180124.wiff.1.idx2ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-320180124.wiff.1.idx2ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-720180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-720180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-820180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-620180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-220180124.wiff.1.idx2ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-320180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-220180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-120180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-820180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-420180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-120180124.wiff.1.idx2ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-520180124.wiffftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-520180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-220180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-320180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-420180124.wiff.1.idx2ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH1-620180124.wiff.scanftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/peptides.pep.xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD010604/CDCTMTH120180124_MGFPeaklist.mgfprimaryOK200002860xinhuazhou9901@163.comxinhua zhouMass SpectrometryShotgun proteomicsAlzheimer's DiseaseNot availableAlzheimer’s disease (ad)Pink1DonepezilAmyloid beta (aβ)Proteomicshttp://www.ebi.ac.uk/pride/archive/projects/PXD010604BrainHippocampal NeuronNeutrophilMice were sacrificed after intraperitoneal injections with 1% pentobarbital for brain collection. Then hippocampus were dissected and lysed with 8 M urea homogenization buffer (8 M urea in PBS, pH 8.0, 1× protease inhibitor cocktail), and homogenized using ultrasonic disruption system. Tissue lysates were centrifuged at 12500 RPM for 15 min at 4 ℃. Protein concentration was measured by Pierce BCA protein assay kit according to the manufacturer’s instructions. Pooled total 100 μg of proteins form six individual sample (pre group), 16.7 μg of proteins form per mouse. The pooled samples were treated with 10 mM dithiothreitol (DTT) for 1 h at 55 ℃, and then incubated with 25 mM idoacetamide (IAA) for 1 h at room temperature in the dark. After that, the sample were diluted with PBS to a final urea concentration of 1.0 M and digested with trypsin/Lys-C (1:25 w/w) (Promega, WI, USA) at 37 ℃ overnight. On the second day, formic acid (FA) was added to acidify the protein to achieve final pH 1-2, followed by centrifugation at 12000 RPM for 10 min at 4 ℃ to collect the supernatant. Then the sample were desalted with reversed-phase column chromatography (Oasis HLB; Waters, MC, USA) according to manufacturer’s instructions, dried under vacuum centrifuge and dissolved in 50 μl triethylammonium bicarbonate buffer (TEAB, 200 mM, pH8.5). Peptides were labeled with TMT reagents according to the manufacturer’s instructions (Thermo Scientific, NJ, USA). Briefly, TMT reagents (0.8 mg TMT dissolved in 40 μl of acetonitrile) was added to the peptide solution and incubated for 1 h at room temperature. Subsequently, 5 μl of 5% hydroxylamine was added to terminate labeling reaction for 15 min at room temperature. Peptides were labeled with different TMT labels: TMT-126, hippocampus or cortex of wild type; TMT-127, hippocampus or cortex of 3×Tg-AD. The peptides solution from wild type and 3×Tg-AD group were mixed, then dried under vacuum centrifuge. TMT labeled peptides mixture was fractionated with high pH reversed-phase peptide fractionation kit according to the manufacturer’s instructions (Thermo Scientific, NJ, USA). Briefly, peptide were dissolved with 300 μl 0.1% FA, and loaded onto an equilibrated, high-pH, reversed-phase fractionation spin column, followed by washing with step gradient of increasing acetonitrile concentrations to elute bound peptides into eight different fractions collected by centrifugation. Each fraction is then dried in a vacuum centrifuge, then dissolved with 0.1% FA for LC-MS/MS analysis.PrideTMTacetylated residueNanoLC-ESI-MS/MS analysis The lyophilized peptides fractions were re-suspended in 2% acetonitrile containing 0.1%formic acid, and loaded on ChromXP C18 (3 μm, 120 Å) trap column. The online Chromatography seperation was performed on the Eksigent nanoLC-Ultra™ 2D System (SCIEX, Concord, ON), the trapping, desalting procedure were carried out at 4μL/min for 5 min with 100% solvent A (water / acetonitrile / formic acid (98 /2 / 0.1%; B, 2 /98 /0.1%)). Then, an elution gradient of 5-38% solvent B in 60 min was used on an analytical column (75 μm x 15 cm C18- 3μm 120 Å, ChromXP, Eksigent). Data acquisition was performed with a TripleTOF 5600+ Mass Spectrometry (SCIEX, Concord, ON) fitted with a Nanospray III source (AB SCIEX, Concord, ON). Data was acquired using an ion spray voltage of 2.4 kV, curtain gas of 35 PSI, nebulizer gas of 12 PSI, and an interface heater temperature of 150℃. The MS was operated with TOF-MS scans. For IDA, survey scans were acquired in 250 ms and up to 40 product ion scans (80ms) were collected if exceeding a threshold of 160 cps with a charge state of 2-5. A Rolling collision energy setting was applied to all precursor ions for collision-induced dissociation. Dynamic exclusion was set for 14 s. Database searching and protein quantification Proteins identification and relative quantification was performed by PEAKS 8.5 software (Bioinformatics Solutions, Waterloo, Canada) .The raw mass spectra were searched against uniprot-mus musculus database containing 51697 protein entries (released in July 2017)with the following setting parameters: parent mass error tolerance of 30 ppm and fragment mass error tolerance of 0.1 Da. Setting enzyme: trypsin, fixed modifications including deamidation (NQ)、oxidation (M)、Pyro-glu from E、Pyro-glu from Q、Acetylation (Protein N-term) and max Variable PTM Per Peptide: 3;The false discovery rate (FDR) was estimated at ≤1.0% at psm (Peptide-Spectrum Matches) level determined by a decoy database search as implement in PEAKS 8.5; peptide score (−10lgP) greater than 19.5, which is equivalent to a P-value of ∼1%, were regarded as confidently identified. Relative quantification of peptides and proteins were performed by the TMT 6plex method in PEAKS Q module, all TMT reporter ion spectra area of identified peptides were summed and taken as the normalized factor across different samples. Statistical analysis of differentially abundant proteins was conducted using Peaks Q algorithm, expression of peptides and proteins were considered to be significantly different between samples when the ratio ≥1.2 or<0.83 and protein significance score ≥5. The ratios of altered proteins in each group were set as group AD/WT, group donepezil/WT. The ratio of changed proteins by donepezil treatment was set as group donepezil/AD. Bioinformatics analysis In this study, the changed proteins were subjected to functional enrichment analysis of Gene Ontology (GO) terms of biological process (BP), molecular function (MF), and cellular components (CC) using DAVID Bioinformatics resources 6.8. The pathway analysis with change proteins were determined using KEGG (Kyoto Encyclopedia of Genes and Genomes) path database(https://www.kegg.jp/kegg/). Heml 1.0 and Graphpad 7.0 was used to heat map analysis. For the protein-protein interaction network analysis, we used STRING database version 10.5 (http://string-db.org/). The interaction network was mapped by Cytoscape (3.6.0).ProteomicsXinhua ZhouTripleTOF 5600State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, MacauPARTIALMus Musculus (mouse)xinhuazhou9901@163.com30484658 Zhou X, Xiao W, Su Z, Cheng J, Zheng C, Zhang Z, Wang Y, Wang L, Xu B, Li S, Yang X, Pui Man Hoi M. Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer's disease and implication of PINK 1 regulation in donepezil treatment. J Proteome Res. 2018 10.1021/acs.jproteome.8b00818Human brain proteome project (hupo_hbpp) (b/d-hpp)University of MacauMacauDonepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APP<sub>Swe</sub>/PSEN1<sub>M146V</sub>/MAPT<sub>P301L</sub>) mouse model (3×Tg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions, and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3×Tg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub>) and senile plaques were reduced in the hippocampus. Golgi staining of the hippocampus showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3×Tg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein-protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR, and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by Western blotting. Donepezil exhibited neuroprotective effects via multiple mechanisms. In particular, PINK 1 is related to mitophagy and cellular protection from mitochondrial dysfunction, which might play important roles in AD pathogenesis and represent a potential therapeutic target.Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment.Zhou Xinhua X, Xiao Wei W, Su Zhiyang Z, Cheng Jiehong J, Zheng Chengyou C, Zhang Zaijun Z, Wang Yuqiang Y, Wang Liang L, Xu Benhong B, Li Shupen S, Yang Xifei X, Pui Man Hoi Maggie Msodium salt, Forms, CPD photolyase activity, ammonium formate, 13C-labeled, cadmium salt, MeCN, PhrB photolyase activity, Laboratory, A4, Basodexan, 2-(indol-3-yl)ethanoic acid, magnesium formate, Apaf-1, House Mouse, zinc salt, Bca, Polypeptides, KL receptor activity, protein polypeptide chains, Formations, cobalt(II) formate dihydrate, CH3-C#N, GRP1, Grp1, SCO5, Urea, 1, 2, AGM4, 3, 4, SCO1, NUP96, Pentobarbital, outer pigmented layer of retina, Gsfsow3, epithelium, (R*, bca, sarcoma of breast, hac-1, weight-weight percentage, PTPSTEP, Tissue, chemical analysis., Processed cyclic AMP-responsive element-binding protein 3-like protein 1, proteins, W, suprasegmental levels of nervous system, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, pigment epithelium of retina, column, sample, Etaminal, 6(1H, pigmented retina epithelium, Bs, s, nickel salt, GPH, LC-MS2, suprasegmental structures, Ammon, BZRP, cobalt (+2) salt, Trypsin/K, anon-53Fa, l(2)SH0173, breast sarcoma, seahorse, PBS, PBR, PBT, (Indol-3-yl)acetate, sodium (4:1:1) salt, Hippocampal, Dm1, magnesium salt, dipyrimidine photolyase (photosensitive), simple tissue, Subiculum, CG6829, cortex of organ, dark/hac-1/dapaf-1, pbt, Caspase-14 subunit p10, CG11628, LY57, Swiss Mouse, formate, Sagatal, pooled, cromium (+3), Caspase-14 subunit p19, Striatum-enriched protein-tyrosine phosphatase, beta Trypsin, w/w, Indole-3-acetic acid, Painful bladder syndrome, heteroauxin, liquid chromatography-tandem mass spectroscopy, ammonium (4:1) salt, Mouse, methyl cyanide, lead (+2) salt, TMT, krk1, BPBS, Old astrocyte specifically-induced substance, Cleland Reagent, Hydroxylamine Hydrochloride, 3.4.22.-, nickel formate dihydrate, GRP1/cytohesin 1, lead formate, sarcoma of the breast, 5H)-Pyrimidinetrione, aluminum salt, Pierce, 4-dimercapto-, mini-ICE, Carbamide, R*)-, protein-containing complex, body system, CG7826, deoxyribodipyrimidine photolyase activity, stratum pigmentosum retinae, CG11633, Ly57, Oasis, LC-MSMS, CG7835, Gene Products, Mus musculus domesticus, CG42273, system, Carmol, MAM, Cornu Ammonis, Hippocampus, anatomical systems, thallium (+1) salt, Ethaminal, Monosodium Salt, beta-Trypsin, rubidium salt, F23A5.3, pk18, methanoic acid, hippocampus major, MBR, Solution, Injectable, PTBR, peptidos, Chromatographies, Horn, 1H-indol-3-ylacetic acid, proto-oncogene c-Kit, dark/dapaf-1/hac-1, mass percentage, grupo, 1-(14)C-labeled, Proper, dApaf-1, Proteins, Hippocampus Propers, Clelands Reagent, Hippocampal Formation, stepk, potassium formate, copper (+2) salt, Mischung, backward, acetonitrile, buffer, encephalon, polypeptide, APAF1, archipallium, Temperatures, native protein, carbonyldiamide, Hac-1, Pentobarbital Sodium, KIT ligand receptor activity, cupric formate, 5-ethyl-5-(1-methylbutyl)-, aluminum formate, Hippocampus Proper, XKrk1, Cleland's, AU020952, RPE, lithium formate, DMDA1, 3-Indolylessigsaeure, OASIS, Dark/Dapaf-1/HAC1, House Mice, CNS - Brain - Hippocampus (MMHCC), ethanenitrile, CD117, mDRC, retinal pigment epithelium, DmelCG11628, ME-IV, p. pigmentosa retinae, Cleland's Reagent, Gene Proteins, hippocampus, C-Kit, Ssm, xkl-1, liquid chromatography tandem mass spectrometry, deoxyribonucleate pyrimidine dimer lyase (photosensitive), reversed, liquid chromatography tandem mass spectroscopy, Hac-1/Dark, NCMe, determination, Ammon horn fields, DmelCG6829, Mus domesticus, zinc formate, lead salt, CASP-14, Xkl-1, protein, pigmented epithelium, peptide, Gsfsco1, ammonium tetraformate, IAA, peptido, ClvPrd, Min, synganglion, Apaf1, protein aggregate, Injectables, Gsfsco5, ARK, DmelCG42273, SOW3, portion of tissue, LCMSMS, peptides, dermoid cyst with malignant transformation, Pentobarbitone, E927b, pigmented retina, min, arc, Swiss Mice, mAPC, IBP, Mebumal, copper, ark, Ammons Horn, DNA cyclobutane dipyrimidine photolyase activity, T1, Hydroxylammonium Chloride, reaction, lithium salt, Sputolysin, Ammons horn, l(2)k08110, 3H, Lyw-57, dApaf1, TEAB, house mouse, Bladder pain syndrome, Sl, ammonium (2:1) salt, ammon gyrus, PRE, D-Apaf-1, formatio hippocampi, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, mouse, LC-MS/MS, Dmel_CG7826, Ammon Horn, Tr-kit, hippocampus proper, pigmented retinal epithelium, Thermo Scientific, ur, Subiculums, SLP65, carbamide, Ly-57, S-adenosyl-L-methionine:thiol S-methyltransferase activity, retinal pigment, Cleland, Mini-ICE, 3.1.3.48, tissue portion, kl1-A, major hippocampus, Ammon's Horn, IES, KIT, nickel (+2) salt, retinal pigment layer, Dmel_CG7835, Mnb, MNB, tyrosine-protein kinase Kit, Mus musculus, SLP-65, ammonium salt, Ammon's, Ammon's horn, Painful Bladder Syndrome, BASH, Step, mice, Xylella fastidiosa str. Temecula1, retinal pigmented epithelium, Encephalon, cobaltous formate, 3-Butanediol, kit, hac1, AW124434, MICE, domesticus, organ system, dapaf-1S, Monosodium Salt Pentobarbital, H2NC(O)NH2, phr A photolyase activity, apaf-1, primal cortex, dapaf-1L, DMDA, DNA-photoreactivating enzyme, STEP, copper salt, Diabutal, Polypeptide, 1728, Bladder Pain Syndrome, Gruppe, the brain, Dapaf-1/HAC-1, Reagent, ammon horn, cesium salt, SCF receptor activity, Gene, photoreactivating enzyme activity, TYPE, LC-MS-MS, Buffer, formic acid, Dark/Hac-1/dApaf1, DAGA4, Karbamid, cytohesin/GRP1, Hac1, potassium salt, Dark/Hac-1/dApaf-1, scfr, polypeptide chain, House, Injection, 14C-labeled, Harnstoff, stratum pigmentosa retinae, Mice, SCFR, SCG3, Pro-Mega, Fdc, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, PRECOCIOUS, Mebubarbital, Swiss, hippocampus (Crosby), dapaf-1, l(2)SH2 0323, Indoleacetic acid, dapaf, labeling, dark, calcium formate, Xylella fastidiosa (strain Temecula1 / ATCC 700964), Neural-specific protein-tyrosine phosphatase, (indol-3-yl)acetic acid, DARK, grupos, cromium (+3) salt, dArk, Dapaf-1, F23A5_3, sodium formate, thiol methyltransferase activity, BLNK-S, Cornu ammonis, DYRK1, nickel formate, DBI, 3H-labeled, protein complex, strontium formate, apaf1, strontium salt, Peptide, group, LGMD2C, cortex, stratum pigmentosum (retina), MODIFIER OF SNC1, LC/MS/MS, PKBS, natural protein, Mus, Protein, deoxyribonucleic photolyase activity, Dyrk1, Dark, Vacuums, connected anatomical system, l(2)SH0323, Nembutal, Dark/Apaf-I, ACETONITRILE, cyanomethane, teratoma with malignant transformation, HLB, CYH1, cornu ammonis, hippocampus proprius, c-KIT, Propers, uree, photolyase activity, urea, CC1, Rest, Tripcellim, dApaf-1/DARK/HAC-1, sample population, chromic formate, UREA, Laboratory Mice, Protein Gene Products, cAMP-responsive element-binding protein 3-like protein 1, Trypure, c-kit, concentration, SCARMD2, calcium salt, Peptid, assay, Laboratory Mouse, Hippocampal Formations, groupe, dAPAF-1, Formation, UltrasonicAlzheimer Senile Dementia, Eranz, Presenile Alzheimer Dementia, Senile, Disease, DmelCG4523, ALZHEIMERS DIS, Early Onset, Acute Confusional Senile Dementia, 1H-Inden-1-one, mouse, 3-dihydro-5, 1-Benzyl-4-((5, E 2020., Focal Onset, Alzheimer's disease, Alzheimer's Dementia, unspecified (disorder), Primary Senile Degenerative Dementia, pink1, [X]Dementia in Alzheimer's disease (disorder), Alzheimer Type, ALZHEIMER DIS, E2020, AD, unspecified, [X]Dementia in Alzheimer's disease, Mus, 2, NOS, CG4523, dPINK1, 6-dimethoxy-2-((1-(phenylmethyl)-4-piperidinyl)methyl)-, Dementia, LATE ONSET ALZHEIMER DIS, Alzheimers, DAT - Dementia Alzheimer's type, dPink1, E-2020, Dementia in Alzheimer's disease, mice, Alzheimer, Donepezil Hydrochloride, Alzheimer's Disease Pathway, PINK, Dementias, Alzheimer Dementia, FOCAL ONSET ALZHEIMERS DIS, Senile Dementia, Late Onset, AD - Alzheimer's disease, Alzheimer Disease, Alzheimer Type Dementia, Aricept, Dementia in Alzheimer's disease (disorder), PINK1, TG, Mouse, ALZHEIMER DIS EARLY ONSET, regulation, 6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride, Alzheimer's Disease, Alzheimer's disease (disorder), house mouse, Presenile, BEST:GH23468, Alzheimers Dementia, Donepezilium Oxalate Trihydrate, Alzheimers disease, Dementia of the Alzheimer's typesodium salt, DmGluClalpha, type 2, ammonium formate, 13C-labeled, posttranslational modification, MeCN, cadmium salt, Materials, dmMOF, ion, Raw, SMC4, Glu, GLU, Irip, l(3)61Ea, magnesium formate, fs(1)M34, P150, NK/GPI., zinc salt, NAALAdase, Solvent, glc, 5730420M11Rik, DmelCG9648, Polypeptides, NAALADase I, protein polypeptide chains, FOLH, Drug Tolerance, 2-Aminoglutaric acid, DmGluT1, cobalt(II) formate dihydrate, Hot, CH3-C#N, dMOF, B1, p150, glu, CG4601, C530001K22Rik, 2, germacrene A synthase activity, Software Engineering, Analysis, WMS, adenomas, CG10850, somitogenic mesoderm, SET, E, posttranslational amino acid modification, L-methionine aminopeptidase activity, F, Analyses, DHO, Membrane glutamate carboxypeptidase, Genomes, Dermal papilla-derived protein 7 homolog, phosphatase 2A inhibitor I2PP2A, DmGLUT1, CG18572, proteins, DrosGluCl, SURGICAL AND MEDICAL PROCEDURES, AI047805, DmelCG4299, PA1, set, column, D1, E 2020, ACT, GLUCL, z, drug tolerance, nickel salt, SGS, Gpi, GluCl, cobalt (+2) salt, unsegmented mesenchyme, immune system tolerance, CG13908, MYH-associated polyposis, single organism process, Procedure, GAST, SH2-B PH domain-containing signaling mediator 1, Spectrum Analysis, not genetically inherited, collisionally activated dissociation, CID, Software Tools, ACMICD, 0074/12, bHLHd7, bHLHd6, bHLHd9, Computer Applications, bHLHd8, sodium (4:1:1) salt, bHLHd5, bHLHd4, magnesium salt, Dm1, Su(b), Algorithm, Computer Applications Software, Ontology Projects, NK|GPI, 6-trans-farnesyl-diphosphate diphosphate-lyase (germacrene-A-forming) activity, Hydrogen Oxide, DmelCG7535, MUTYH-associated polyposis, MUTYH-related AFAP, RUTBC3, Ontology, Software Applications, HLA-DR-associated protein II, Dm-GluCl, DmelCG43946, Projects, DI-2, Source Software, I-2Dm, FGCP, formate, proportionality, Spectrometry, cromium (+3), rate, inhibitor of granzyme A-activated DNase, beta Trypsin, Apc5, APC5, I-2PP1, Pro-rich, Applications, TAF-IBETA, Self Tolerance, Material, multiple colorectal, ammonium (4:1) salt, MUTYH-related attenuated familial polyposis coli, TAF-Ibeta, methyl cyanide, lead (+2) salt, TMT, Bglap-rs1, Computer Software Applications, l(1)Ab, glutamic acid, nickel formate dihydrate, lead formate, p150/glued, False, aluminum salt, 3-dihydro-5, mouse <Mus musculus>, 2-trans, precursor, protein-containing complex, body system, Gene Ontology Project, CG7826, Gene Ontology, E2020, DmelCG3025, DmSMC4/gluon, CG7835, Gene Products, CG42273, system, Pgi, DmGlu, Application, MAP, Glutamic acid, Open Source Softwares, proportion, network topology analysis, MAX, anatomical systems, thallium (+1) salt, interventionDescription, Gpi-1r, Software Application, Gpi-1s, familial adenomatous polyposis 2, Phi, rubidium salt, beta-Trypsin, Gpi-1t, Open Source Software, 2pp2a, DmelCG10850, methanoic acid, ESI, ions, CG10574, Solution, Computer Software Application, fs(1)829, max, 2PP2A, Tools, DmelCG18572, dSET, dSet, CT23049, peptidos, Chromatographies, Donepezilium Oxalate Trihydrate, PTHB1, DrosGluCl-alpha1, molecular function unknown, BcDNA:LD20207, CPS, grupo, 1-(14)C-labeled, Proteins, CG3025, 1-Benzyl-4-((5, CG1086, potassium formate, copper (+2) salt, MF, acetonitrile, (+)-(10R)-germacrene A synthase activity, Amf, Tool, Dmel_CG13908, polypeptide, p150[Glued], Temperatures, native protein, Immune Tolerance, I-2PP2A, C18, Glutamate, cupric formate, MUTYH-related attenuated FAP, chemical analysis, Dm I-2, MFS1, segmental plate, GluCla, aluminum formate, Glutaminsaeure, Sh2bpsm1, Mass Spectrum Analyses, NK, Intervention, AU020952, Ontology Project, DL-Glutaminic acid, lithium formate, Col4a-1, E-2020, PYR1, ethanenitrile, post-translational amino acid modification, Folate hydrolase 1, ME-IV, plan specification, Computer Programs, Gene Proteins, 4732433M03Rik, Applications Softwares, quotient, DRORUD, MAP syndrome, Gluon, l(3)L1H, 19.5, Immunological Tolerance, SH2-Bb, Eranz, D1Ucla3, IPP2A2, Bru, Gene Ontology Projects, NCMe, single-organism process, determination, methionine aminopeptidase activity, zinc formate, lead salt, protein, Dmel_CG1086, csp2, peptide, Glt1, ammonium tetraformate, peptido, ClvPrd, Project, Heat, Min, 3.4.17.21, protein aggregate, Gpi-1, Computer Program, DmelCG42273, t1, peptidase M activity, dGluCl-alpha, Mass Spectrum Analysis, Svc, SH2-B, rabGAPLP, PPG, peptides, BcDNA:HL07853, dermoid cyst with malignant transformation, TAF-I, Nlk, dMax, Open, min, Computer Programs and Programming, RabGAP-5, mAPC, NAALAD1, copper, Estimated, Folylpoly-gamma-glutamate carboxypeptidase, Dmglut1, IGAAD, DmSMC4, lithium salt, DmelCG10574, RUSC3, ppm, physiological process, C16orf53, CG7535, Glutaminic acid, house mouse, GPHYSD2, ammonium (2:1) salt, DrosGlu-Cl-alpha, ratio, (+)-germacrene A synthase activity, phapii, Ida, IDA, PLATEST, T5E21.12, 1H-Inden-1-one, mouse, Dmel_CG7826, CG9648, autosomal recessive familial adenomatous polyposis, StF-IT-1, Maps, Source Softwares, Programs, Spectroscopy, Program, S-adenosyl-L-methionine:thiol S-methyltransferase activity, mOC-X, Ionen, PSM, Psm, p150/Glued, dmax, Computer Applications Softwares, Immunologic Tolerance, Genetic Materials, Softwares, presumptive somite mesoderm, Prostate-specific membrane antigen, GAS, nickel (+2) salt, fixed, GAT, Dmel_CG7835, DYNA_DROME, Genetic Material, CG11397, T5E21_12, autosomal recessive, Mnb, MNB, parent ion, Gene Ontologies, ammonium salt, Pteroylpoly-gamma-glutamate carboxypeptidase, ORG, Org, PTM, Ontologies, cobaltous formate, Gpi1-r, Gpi1-s, CG4299, MASS, gas, AW124434, Gpi1-t, RABGAP5, organ system, BcDNA.LD20207, nanospray, GLP-1, MOF, Mof, precursor ion, Tolerance, post-translational modification, Aricept, copper salt, PSMA, Hot Temperatures, Cistron, Polypeptide, l(3)SH7, anon-WO0118547.156, i2pp2a, P150[Glued], Platelets, Gruppe, Gpi1s, DL-Glutamic acid, SH2 domain-containing protein 1B, AI461847, l(3)S007412, cesium salt, unsegmented paraxial mesoderm, FBN, Gene, CG9206, Spectrum Analyses, Computer, somitomeric mesoderm, GCPII, PHAPII, formic acid, Intervention or Procedure, method, potassium salt, dSMC4, template-activating factor I, polypeptide chain, ECTOL1, 14C-labeled, method used in an experiment, Mass, N-acetylated-alpha-linked acidic dipeptidase I, mKIAA1299, Del(8)44H, familial adenomatous polyposis, Mass Spectroscopy, 6-dimethoxy-2-((1-(phenylmethyl)-4-piperidinyl)methyl)-, study, SH2B, Genetic, DmelCG11397, iones, ipp2a2, Interventional, mGCP, posttranslational protein modification, calcium formate, OCTD, autosomal recessive multiple colorectal adenomas, DrosGluCl-alpha, 10^[-6], taf-ibeta, grupos, cromium (+3) salt, molecular function, sodium formate, statistical analysis, thiol methyltransferase activity, Applications Software, Intervention Strategies, Open Source, MUTYH-related attenuated familial adenomatous polyposis, DYRK1, data, Encyclopedias, Computer Software, MUTYH-Associated Polyposis, nickel formate, 3H-labeled, protein complex, 6-trans-farnesyl-diphosphate diphosphate-lyase [(+)-germacrene-A-forming] activity, igaad, strontium formate, strontium salt, Cistrons, Peptide, GCP2, group, AI875693, Glutamate carboxypeptidase II, Software Tool, Cell growth-inhibiting gene 27 protein, CAD, DmelCG9206, natural protein, Protein, p150[glued], I2PP2A, l(3)63Fb, glut1, Dyrk1, connected anatomical system, Software, biological process, ACETONITRILE, cyanomethane, Data Base, WMS2, teratoma with malignant transformation, Mass Spectrum, Temperature, 2-aminopentanedioic acid, PH and SH2 domain-containing signaling mediator, CC1, FCP-D, Engineering, Donepezil Hydrochloride, Tripcellim, Rest, MYH-Associated Polyposis, l(2)k08819, chromic formate, Protein Gene Products, Trypure, dSET/TAF-Ibeta, 2610030F17Rik, CG43946, Ion, SSKS, AA960152, AI425885, calcium salt, Peptid, 6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride, assay, variable, AA407739, groupe, FAP2, colorectal adenomatous polyposisprojections, D430023G06Rik, DmErk, extracellular signal-regulated kinase activity, 2610315D21Rik, pp44mapk, Laboratory, mFLJ00387, Physical, macromitophagy, House Mouse, mE1c-long, DmTOR, Prp4 protein kinase activity, protein polypeptide chains, systemic amyloidosis, LeMPK3, Formations, ATP-protein transphosphorylase activity, p44mpk, ATP:protein phosphotransferase (non-specific) activity, Dp38, 2, RAFT1, Mammalian target of rapamycin, SAPK2, SEM, Sem, insoluble, MAP-k, amyloidosis, kus, beta1tub, CG9277, dPink1, pp42, dmAChE, Neuronal Pathfinding, T, beta-particle, Dsor2, Aches, proteins, elevated, sem, ACEE, AChE, ACE, AU042772, Cognitions, e, decreased, e-, beta1Tub, Axon, medicine, Functions, E 2020, Homo sapiens disease, AW557854, single organism signaling, AchE, p82 kinase activity, ERK-A, CHE, ace, anatomical protrusion, Ammon, dpERK, dpErk, Crushing Pains, Neural Guidance, betaIIPKC, DmMAPK, E 2020., PMK-2, dp-ERK, PMK-1, seahorse, PMK-3, Ache, Wee-kinase activity, dendrite spine, Pains, soluble, Hippocampal, shelf, pMAPK, pMapK, ache, FLOWERING TIME CONTROL PROTEIN FCA ALPHA, CG4523, Braindruse, dPINK1, Subiculum, l(3)26, n-ache, Industrial, Amyloid Substance, DmERKA, amyloidoses, Nerve Cells, Industrial Arts, rl/MAPK, Caspase-14 subunit p10, Rapamycin and FKBP12 target 1, Swiss Mouse, non-specific serine/threonine protein kinase activity, Caspase-14 subunit p19, l(2)41Ac, projection, ridge, Radiating, beta1-tub, beta(-), DTB2, CT34260, dpERk, serine-specific protein kinase activity, ace-2, i6, DL4180C, Cells, HIPK2, SAPK, cytidine 3', Mouse, Physical Suffering, beta-Tub56D, Wee 1-like kinase activity, axon chemotaxis, Specbeta, Acetylthiocholinesterase, Burning Pain, 3.4.22.-, mKIAA0756, glycogen synthase A kinase activity, PARK6, Peptidomics, N-ACHE, lamellae, glycogen synthase kinase 3 activity, Nerve, 3-dihydro-5, e(-), number, 12559, mini-ICE, Radiating Pain, Amyloid Fibril, protein-containing complex, Sufferings, process of organ, phosphorylase b kinase kinase activity, EK2-1, E2020, lamella, B-spec, disease or disorder, Mus musculus domesticus, amyloid, TOR, ribosomal protein S6 kinase II activity, Cornu Ammonis, Suffering, Hippocampus, Erk, ERK, protein-serine kinase activity, Bx34, Pathfinding, Elektron, stubby dendritic spine, STK32, BB138278, beta1t, PINK, tor, Tpr, TPR, hippocampus major, erk, Cognitive Functions, anon-EST:fe1B3, drugs, protein-cysteine kinase activity, mushroom dendritic spine, Hpr kinase activity, Neuron, rll, CG5870, STK26, p38-2, Donepezilium Oxalate Trihydrate, laminae, Frap1, high elevation, myelin basic protein kinase activity, inhibitors, Horn, Axonal Pathfinding, beta-tubulin56D, Dmbeta1, anatomical process, Proper, disorders, stress-activated kinase activity, Hippocampus Propers, MAP-2 kinase activity, 1-Benzyl-4-((5, Hippocampal Formation, FRAP1, FRAP2, mTOR, protein serine kinase activity, i168, mE1d', Cell, protein phosphokinase activity, archipallium, PKA, native protein, PKC, stress-activated protein kinase activity, chemical analysis, mapk2, Mitochondrial Degradation, mapk1, condition, Neurite Guidance, NF, amyloid disease, protein kinase p58 activity, organ process, Hippocampus Proper, Fibril, serine/threonine protein kinase activity, DmelCG5870, CG12559, underdeveloped, E-2020, beta[[1]]-tubulin, dpERK1, Function, b spectrin, Neuritic plaques, House Mice, beta1, CNS - Brain - Hippocampus (MMHCC), FRAP, dsk1, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, beta, signalling, Tub, processes, hippocampus, Fibrils, Senile druse, CT16317, signalling process, dpMAPK, MTOR, BETA, PINK1, mitophagy, 1190006F07Rik, quantitative, mE1c, mE1d, mE1a, mE1b, protein serine-threonine kinase activity, SAP kinase activity, mE1e, FBgn0000024, glycogen synthase kinase activity, Eranz, Cognitive Function, CG17907, DmelCG4523, protein kinase A activity, determination, Ammon horn fields, FKBP12-rapamycin complex-associated protein, Mpk2, Mus domesticus, DELTA AND GAMMA, AA387016, p42mapk, Splitting Pain, CASP-14, protein, thin dendritic spine, betaTub1, l(2)k03905, SR2-1, Hydrolase, B1t, 3.1.1.7, diseases, kinase-related transforming protein, diseases and disorders, Migratory, mitogen-activated protein kinase activity, Acetylcholine Hydrolase, sessile dendritic spine, protein aggregate, present in fewer numbers in organism, mpk1, Mlck, human disease, Erk/Map kinase, hypoplasia, DERK-A, BRPK, Swiss Mice, E(sina)7, Substance, Amyloid, Rl, Ammons Horn, dtor, Raf kinase activity, 1t, MLCK, serine kinase activity, MP kinase activity, DERK, 9830004H17Rik, atypical protein kinase C activity, Ammons horn, papilla, signaling process, MBP kinase II activity, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, TG, dERK, BEST:GH23468, Nerve Cell, KMLC, dTOR, dTor, FK506-binding protein 12-rapamycin complex-associated protein 1, DmAChE, ammon gyrus, Mechanistic target of rapamycin, MAP kinase 2 activity, BETA 56D, Mapk, formatio hippocampi, Arts, 1H-Inden-1-one, lamina, mouse, Erk1, flanges, ERK1, Ammon Horn, mapk1a, ERK2, Physical Sufferings, hippocampus proper, results, Subiculums, M phase-specific cdc2 kinase activity, Amyloid Fibrils, Crushing Pain, Acetylcholine acetylhydrolase, l(1)G0108, Neural Pathfinding, MLCK2, MapK, mapk1b, MAPK, Mini-ICE, Diseases, major hippocampus, Ammon's Horn, axon pathfinding, serine protein kinase activity, erk2, RAPT1, mapk, Mus musculus, beta-tub, phosphorylase B kinase kinase activity, ERKa, Ammon's, Ammon's horn, Beta <eudicots>, BcDNA:RE08694, protein glutamyl kinase activity, l(2R)EMS45-39, mice, shelves, DmelCG12559, Pain, FCAALL.331, p38, axon growth cone guidance, beta56D, Splitting Pains, DmelCG9277, mitochondrion disassembly, MICE, skMLCK, domesticus, DpErk, DpERK, ErkA, disease, beta-Tub, ERKA, hydroxyalkyl-protein kinase activity, WEE1Hu, primal cortex, Radiating Pains, Patient, spine, 5092, epsilon PKC, Aricept, Burning, Klmc, betaTub, pERK, beta1-Tubulin, other disease, ribosomal S6 protein kinase activity, biological signaling, calcium/phospholipid-dependent protein kinase activity, GroupII, CG5092, ammon horn, Migratory Pains, electron, YT, AcChE, presence, l(2)k17004, DmelCG17907, protrusion, pink1, reduced, polypeptide chain, House, subnumerary, branched dendritic spine, betaspec, serine(threonine) protein kinase activity, tiny, Mice, 6-dimethoxy-2-((1-(phenylmethyl)-4-piperidinyl)methyl)-, DmelCG8274, T-antigen kinase activity, galactosyltransferase-associated kinase activity, study, betatub(56D), Swiss, hippocampus (Crosby), xp42, amyloidosis (disease), beta[[1]] tubulin, inhibiteur, flat, ridges, decreased number, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, non-neoplastic, Neuronal Guidance, protein kinase (phosphorylating) activity, inhibidor, SPEC8, Raf-1, Clients, Splitting, disorder, Burning Pains, DmERK-A, casein kinase (phosphorylating) activity, Acetylcholine, CT24817, dAChE, small, Spec-beta, Cornu ammonis, ert1, Axon Pathfinding, protein complex, prkm2, prkm1, CT39192, Tubulin, inhibitor, medical condition, FRAP/TOR, DmelCG5092, Client, cognitive function, p38delta, count in organism, 2.7.11.1, twitchin kinase activity, natural protein, arache, Mus, Protein, AP50 kinase activity, MBP kinase I activity, betaSpec, b-Spec, flange, Xp42, mitochondrion degradation, threonine-specific protein kinase activity, cornu ammonis, l(1)G0074, hippocampus proprius, Crushing, l(1)G0198, Propers, negatron, l(3)87Ed, mitogen activated kinase activity, Su(Raf)2B, Donepezil Hydrochloride, CT24745, Rapamycin target protein 1, AI327068, EY2-2, Cognitive, Migratory Pain, ARACHE, Laboratory Mice, process, D-ERK, beta-spec, CG8274, processus, 6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride, assay, Laboratory Mouse, Hippocampal Formations, Spec, Formation, NRCAML, A-kinase activity, MAP kinase 1 activity, presence or absence in organismAmyloid intracellular domain 57, D430023G06Rik, Amyloid intracellular domain 59, Presenile Alzheimer Dementia, 2610315D21Rik, AW554487, Laboratory, Early Onset, A4, macromitophagy, AChEI, Amyloid intracellular domain 50, House Mouse, Alzheimer's disease, DmTOR, AAA, Cvap, AD, unspecified, CG42318, systemic amyloidosis, AG, DmelCG12298, Formations, DDPAC, 2, SCRAMBLED, acetylcholine acetylhydrolase inhibitors, RAFT1, Mammalian target of rapamycin, AID(50), insoluble, acetyl.beta-methylcholinesterase inhibitors, amyloidosis, modification by symbiont of host biological process, Ag, kus, beta1tub, stimulation by symbiont of host programmed cell death, CG9277, dPink1, Neuronal Pathfinding, Tissue, T, beta-particle, proteins, elevated, Golgi, Alzheimer disease amyloid A4 protein homolog, N-APP, Gamma-secretase C-terminal fragment 50, e, decreased, e-, beta1Tub, Axon, Gamma-secretase C-terminal fragment 57, Gamma-secretase C-terminal fragment 59, AD1, E 2020, AD3, Homo sapiens disease, Alzheimers disease, Histological Labeling, Ammon, S-APP-alpha, Neural Guidance, Acute Confusional Senile Dementia, EC 3.1.1.7 (acetylcholinesterase) inhibitors, STRUBBELIG, CG17144, Alzheimer's Dementia, seahorse, Alzheimer Type, dendrite spine, enhancement of host programmed cell death, soluble, Hippocampal, Playthings and Play, AI551861, choline esterase I inhibitor, FLOWERING TIME CONTROL PROTEIN FCA ALPHA, CG4523, Braindruse, true cholinesterase inhibitor, dPINK1, Subiculum, haemolysis in host, Dementia, Cerebral vascular amyloid peptide, Amyloid Substance, amyloidoses, Nerve Cells, Caspase-14 subunit p10, Alzheimer, Rapamycin and FKBP12 target 1, acetylcholine esterase inhibitor, Swiss Mouse, NRAS, perturbation by symbiont of host defense response, Caspase-14 subunit p19, FTDP-17, beta1-tub, beta(-), DTB2, regulation of cytolysis of host cells by symbiont, choline esterase I inhibitors, Senile Dementia, hyaline, induction by symbiont of host programmed cell death, hemolysis by symbiont of host red blood cells, i6, DL4180C, activation by symbiont of host programmed cell death, Cells, MAPTL, acetylthiocholinesterase inhibitors, Mouse, Alzheimer's Disease, beta-Tub56D, axon chemotaxis, Specbeta, 3.4.22.-, mKIAA0756, amyloid-beta A4 protein, DmelCG42318, Peptidomics, regulation by symbiont of host system process, modulation by organism of defense response of other organism involved in symbiotic interaction, Nerve, 3-dihydro-5, number, e(-), mini-ICE, Amyloid Fibril, Focal Onset, betaApp, unspecified (disorder), AID(59), E2020, ALZHEIMER DIS, [X]Dementia in Alzheimer's disease, B-spec, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, Gene Products, disease or disorder, protease nexin-II, Mus musculus domesticus, ALPS4, amyloid, TOR, Cornu Ammonis, MAP kinase cascade, Hippocampus, Toy, Bx34, Pathfinding, PreA4, Playthings, mei-1794, Elektron, MAPK signaling, stubby dendritic spine, BB138278, beta1t, PINK, S-APP-beta, Dmel_CG17144, CG5620, tor, Tpr, TPR, Gamma-CTF(59), hippocampus major, X-PS-beta, anon-EST:fe1B3, AID(57), Golgi ribbon, Puppets, true cholinesterase inhibitors, MAP kinase kinase kinase cascade, mushroom dendritic spine, KC1epsilon, Neuron, CG5870, Donepezilium Oxalate Trihydrate, Frap1, high elevation, Puppet, Drl, Horn, Axonal Pathfinding, beta-tubulin56D, Dmbeta1, Amyloidogenic glycoprotein, disruption by symbiont of host cell, acetylcholine acetylhydrolase inhibitor, NRAS1, hemolysin activity, Proper, Proteins, disorders, Hippocampus Propers, 1-Benzyl-4-((5, Hippocampal Formation, Golgi complex, FRAP1, Stainings, FRAP2, mTOR, backward, i168, Cell, S182, Mdu, archipallium, mda, chemical analysis, Mitochondrial Degradation, condition, Neurite Guidance, NF, ami, amyloid disease, Hippocampus Proper, Fibril, DmelCG5870, enhancement of host programmed cell death by organism, underdeveloped, E-2020, beta[[1]]-tubulin, med, Dub, b spectrin, Neuritic plaques, AcCholE inhibitors, House Mice, beta1, CNS - Brain - Hippocampus (MMHCC), cholinesterase inhibitors, FRAP, beta, C31, Tub, Gene Proteins, hippocampus, Fibrils, Senile druse, activation by organism of host programmed cell death, acetylcholinesterase (EC 3.1.1.7) inhibitors, CT16317, acetylcholinesterase inhibitor, Dementia in Alzheimer's disease (disorder), MTOR, BETA, PINK1, mitophagy, Beta-APP42, PN2, quantitative, Beta-APP40, biopsy, reversed, ABPP, Eranz, APP, ABETA, DmelCG4523, ALZHEIMERS DIS, Ad3h, determination, Ammon horn fields, ERK/MAPK cascade, FKBP12-rapamycin complex-associated protein, Mus domesticus, positive regulation by symbiont of host non-apoptotic programmed cell death, DELTA AND GAMMA, CTFgamma, AA387016, CASP-14, thin dendritic spine, betaTub1, l(2)k03905, Abpp, CG11121, SUB, EC 3.1.1.7 inhibitor, B1t, old, diseases, Beta-amyloid protein 42, cerebral vascular amyloid peptide, hemolysis by symbiont of host RBCs, cholinesterase inhibitor, Beta-amyloid protein 40, pathogenesis, diseases and disorders, cytopathology, amyloidogenic glycoprotein, sessile dendritic spine, present in fewer numbers in organism, KIF20A, NCMS, Mlck, LATE ONSET ALZHEIMER DIS, N-ras, human disease, PPI, DAT - Dementia Alzheimer's type, hypoplasia, Swiss Mice, Apnh, Substance, Amyloid, SO, Ammons Horn, dtor, activation by organism of programmed cell death in other organism during symbiotic interaction, 1t, MLCK, 9830004H17Rik, AD - Alzheimer's disease, Ammons horn, MAPKKK cascade during sporulation, Alzheimer Type Dementia, Pathologies, PPP1R103, TG, Abeta, ALZHEIMER DIS EARLY ONSET, X-PS-alpha, APPI, cytolysis by organism of host cells, Presenile, BEST:GH23468, Nerve Cell, C80, KMLC, AI413597, So, dTOR, dTor, FK506-binding protein 12-rapamycin complex-associated protein 1, C83, swe, ammon gyrus, Mechanistic target of rapamycin, Senile, BETA 56D, AICD-50, formatio hippocampi, Mtapt, PS1, 1H-Inden-1-one, mouse, Ammon Horn, CR32097, Labeling and Staining, hippocampus proper, Gamma-CTF(57), positive regulation by symbiont of host programmed cell death, MAPK signal transduction, Subiculums, C99, Amyloid Fibrils, l(1)G0108, Neural Pathfinding, MLCK2, acetylcholine hydrolase inhibitors, Mini-ICE, Diseases, AICD-57, modulation by symbiont of host system process, Plaything, MSTD, major hippocampus, NOS, Ammon's Horn, axon pathfinding, RAPT1, upregulation by symbiont of host programmed cell death., AICD-59, acetylcholinesterase (EC 3.1.1.7) inhibitor, PS-1, Mus musculus, beta-tub, Ammon's, Alzheimers, Ammon's horn, histopathology, Beta <eudicots>, mice, acetylcholine hydrolase inhibitor, Toys, FCAALL.331, Dementias, amyloid precursor protein, axon growth cone guidance, alzheimer disease amyloid A4 protein homolog, Alzheimer disease amyloid protein, beta56D, DmelCG9277, mitochondrion disassembly, Protease nexin-II, MICE, skMLCK, Dmel_CG5620, induction by organism of programmed cell death in other organism during symbiotic interaction, modification by symbiont of host morphology or physiology, domesticus, pre-pulse inhibition, disease, beta-Tub, Mitochondrial dysfunction, primal cortex, Labelings, FAD, 5092, MAPK signalling, Aricept, EC 3.1.1.7 inhibitors, Klmc, AV095280, amyloid-beta (A4) precursor protein, betaTub, beta1-Tubulin, Dementia of the Alzheimer's type, AT1G11140, protein levels, other disease, Plays, P3(40), CG5092, ammon horn, Histological Labelings, NS6, amyloid beta A4 protein, Gene, electron, presence, l(2)k17004, acetyl.beta-methylcholinesterase inhibitor, CG12298, AW045860, pink1, reduced, House, DmelCG11121, subnumerary, branched dendritic spine, APP-C57, betaspec, APP-C59, alzheimer disease amyloid protein, Histological, tiny, Mice, 6-dimethoxy-2-((1-(phenylmethyl)-4-piperidinyl)methyl)-, DmelCG8274, induction of non-apoptotic programmed cell death by other organism, somda, betatub(56D), AcCholE inhibitor, Staining, Swiss, hippocampus (Crosby), amyloidosis (disease), beta[[1]] tubulin, acetylcholinesterase inhibitors, flat, CK1epsilon, decreased number, FOCAL ONSET ALZHEIMERS DIS, non-neoplastic, AW457082, Neuronal Guidance, AI426939, SPEC8, Alzheimer Disease, Play, disorder, SRF9, Alzheimer's disease (disorder), Alzheimers Dementia, CT24817, MTBT1, MTBT2, small, Alzheimer Senile Dementia, Spec-beta, Cornu ammonis, Disease, MAPKKK cascade, Axon Pathfinding, activation by organism of non-apoptotic programmed cell death in other organism, Tau, TAU, E030013M08Rik, PPND, Tubulin, medical condition, FRAP/TOR, mitogen-activated protein kinase cascade, DmelCG5092, Labeling, Primary Senile Degenerative Dementia, [X]Dementia in Alzheimer's disease (disorder), Gamma-CTF(50), STRUBBELIG-RECEPTOR FAMILY 9, APP-C99, count in organism, 2.7.11.1, tau, Mus, Adap, Protein, CMNS, modulation by symbiont of host defense response, betaSpec, induction by organism of programmed cell death in other organism involved in symbiotic interaction, mitigation by symbiont of host defense response, b-Spec, CKIe, mitochondrion degradation, cornu ammonis, P3(42), PN-II, l(1)G0074, hippocampus proprius, l(1)G0198, Propers, negatron, acetylthiocholinesterase inhibitor, Dementia in Alzheimer's disease, Donepezil Hydrochloride, Alzheimer's Disease Pathway, CT24745, Rapamycin target protein 1, Soluble APP-beta, AI327068, Alzheimer Dementia, mg/kg, Laboratory Mice, Protein Gene Products, Nhe1, Late Onset, clear, beta-spec, CG8274, Soluble APP-alpha, 6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride, assay, T19D16.8, Laboratory Mouse, Hippocampal Formations, SCM, Spec, CVAP, Formation, NRCAML, presence or absence in organismEranz, other disease, DmelCG4523, Proteins, 1H-Inden-1-one, mouse, disorders, 3-dihydro-5, Gene, 1-Benzyl-4-((5, medical condition, E 2020., Concept, pink1, E2020, Role Concept, diseases, Mus, Roles, Protein, Diseases, Role, Gene Products, disease or disorder, Concepts, condition, 2, diseases and disorders, CG4523, dPINK1, 6-dimethoxy-2-((1-(phenylmethyl)-4-piperidinyl)methyl)-, human disease, dPink1, E-2020, mice, Donepezil Hydrochloride, PINK, proteins, non-neoplastic, Protein Gene Products, Gene Proteins, disease, Aricept, Role Concepts, E 2020, disorder, PINK1, TG, Homo sapiens disease, Mouse, 6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride, house mouse, BEST:GH23468, Donepezilium Oxalate Trihydrate286trueHippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease: insights into the role of PINK 1 proteins in donepezil treatment Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease: insights into the role of PINK 1 proteins in donepezil treatmentDonepezil, an acetylcholinesterase (AChE) inhibitor, was approved by FDA for the symptomatic therapies of patients with Alzheimer’s disease (AD) in 1996. Although donepezil have been regarded as the standard and first-line treatment for AD, the capacity of such drugs to alter the underlying disease process is still unclear. In this study, we sought to explore the possible protective mechanism of donepezil in triple-transgenic Alzheimer’s disease (3×Tg-AD) mice model. 3×Tg-AD mice were treated for 4 months with donepezil (1.3 mg /kg) and its effects were evaluated by behavioral tests and molecular analysis. The cognition of donepezil-treated mice was restored significantly. Reduced levels of soluble and insoluble amyloid beta 1-40 (Aβ 1-40) and amyloid beta 1-42 (Aβ 1-42) as well as senile plaques were observed. Moreover, donepezil treatment prevented the dendritic spine loss in hippocampus neurons. We further investigated the effects of donepezil on the hippocampal protein of 3×Tg-AD mice by quantitative proteomics technology. Proteomic results indicated that donepezil significantly elevated the levels of PINK1, NFASC, MYLK2, and RASN in the hippocampus, and modulated axon guidance, mitophagy, mTOR signaling, and MAPK pathway. The results suggested that donepezil induced neuroprotective effects through multiple 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