{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":47,"searchCount":0},"additional":{"submitter":["Elliott-Hunt CR"],"funding":["NIA NIH HHS","Medical Research Council","Wellcome Trust"],"pagination":["455-62"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3145121"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(3)"],"pubmed_abstract":["Expression of the neuropeptide galanin is known to be upregulated in the brain of patients with Alzheimer's disease (AD). We and others have shown that galanin plays a neuroprotective role in a number of excitotoxic injury paradigms, mediated by activation of the second galanin receptor subtype (GAL2). In the present study, we investigated whether galanin/GAL2 plays a similar protective role against amyloid-β(Aβ) toxicity. Here we report that galanin or the GAL2/3-specific peptide agonist Gal2-11, both equally protect primary dispersed mouse wildtype (WT) neonatal hippocampal neurons from 250 nM Aβ1-42 toxicity in a dose dependent manner. The amount of Aβ1-42 induced cell death was significantly greater in mice with loss-of-function mutations in galanin (Gal-KO) or GAL2 (GAL2-MUT) compared to strain-matched WT controls. Conversely, cell death was significantly reduced in galanin over-expressing (Gal-OE) transgenic mice compared to strain-matched WT controls. Exogenous galanin or Gal2-11 rescued the deficits in the Gal-KO but not the GAL2-MUT cultures, confirming that the protective effects of endogenous or exogenous galanin are mediated by activation of GAL2. Despite the high levels of endogenous galanin in the Gal-OE cultures, the addition of exogenous 100 nM or 50 nM galanin or 100 nM Gal2-11 further significantly reduced cell death, implying that GAL2-mediated neuroprotection is not at maximum in the Gal-OE mice. These data further support the hypothesis that galanin over-expression in AD is a neuroprotective response and imply that the development of a drug-like GAL2 agonist might reduce the progression of symptoms in patients with AD."],"journal":["Journal of Alzheimer's disease : JAD"],"pubmed_title":["Endogenous galanin protects mouse hippocampal neurons against amyloid toxicity in vitro via activation of galanin receptor-2."],"pmcid":["PMC3145121"],"funding_grant_id":["P01 AG009466","R01 AG010668","AG10668","G1000863","P01 AG014449","G0300028","R01 AG043375","081485"],"pubmed_authors":["Elliott-Hunt CR","Hartley DM","Perez S","Mufson EJ","Wynick D","Holmes FE"],"view_count":["47"],"additional_accession":[]},"is_claimable":false,"name":"Endogenous galanin protects mouse hippocampal neurons against amyloid toxicity in vitro via activation of galanin receptor-2.","description":"Expression of the neuropeptide galanin is known to be upregulated in the brain of patients with Alzheimer's disease (AD). We and others have shown that galanin plays a neuroprotective role in a number of excitotoxic injury paradigms, mediated by activation of the second galanin receptor subtype (GAL2). In the present study, we investigated whether galanin/GAL2 plays a similar protective role against amyloid-β(Aβ) toxicity. Here we report that galanin or the GAL2/3-specific peptide agonist Gal2-11, both equally protect primary dispersed mouse wildtype (WT) neonatal hippocampal neurons from 250 nM Aβ1-42 toxicity in a dose dependent manner. The amount of Aβ1-42 induced cell death was significantly greater in mice with loss-of-function mutations in galanin (Gal-KO) or GAL2 (GAL2-MUT) compared to strain-matched WT controls. Conversely, cell death was significantly reduced in galanin over-expressing (Gal-OE) transgenic mice compared to strain-matched WT controls. Exogenous galanin or Gal2-11 rescued the deficits in the Gal-KO but not the GAL2-MUT cultures, confirming that the protective effects of endogenous or exogenous galanin are mediated by activation of GAL2. Despite the high levels of endogenous galanin in the Gal-OE cultures, the addition of exogenous 100 nM or 50 nM galanin or 100 nM Gal2-11 further significantly reduced cell death, implying that GAL2-mediated neuroprotection is not at maximum in the Gal-OE mice. These data further support the hypothesis that galanin over-expression in AD is a neuroprotective response and imply that the development of a drug-like GAL2 agonist might reduce the progression of symptoms in patients with AD.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011","modification":"2024-11-10T04:44:44.11Z","creation":"2019-03-27T03:07:27Z"},"accession":"S-EPMC3145121","cross_references":{"pubmed":["21471641"],"doi":["10.3233/jad-2011-110011","10.3233/JAD-2011-110011"]}}