biostudies-literatureCausevic MDeutscher Akademischer Austauschdienst (DE)Breuer Foundation Alzheimer AwardHelmholtz-Israel projectMinistarstvo Obrazovanja, Znanosti i SportaEU Joint Programme for Neurodegenerative Disease ResearchCenters of Excellence in Neurodgeneration (CoEN) initiativeHrvatska Zaklada za Znanoste0200344https://www.ebi.ac.uk/biostudies/studies/S-EPMC6034874biostudies-literatureUnknown13(7)It is intriguing that a rare, inherited lysosomal storage disorder Niemann-Pick type C (NPC) shares similarities with Alzheimer's disease (AD). We have previously reported an enhanced processing of β-amyloid precursor protein (APP) by β-secretase (BACE1), a key enzyme in the pathogenesis of AD, in NPC1-null cells. In this work, we characterized regional and temporal expression and processing of the recently identified BACE1 substrates seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), and APP, in NPC1-/- (NPC1) and NPC1+/+ (wt) mouse brains. We analysed 4-weeks old brains to detect the earliest changes associated with NPC, and 10-weeks of age to identify changes at terminal disease stage. Sez6 and Sez6L were selected due to their predominant cleavage by BACE1, and their potentialPloS oneBACE1-cleavage of Sez6 and Sez6L is elevated in Niemann-Pick type C disease mouse brains.PMC6034874RiModFTD2016-2017.IP-2016-06-2799Cermak SHavas DHecimovic SWindisch MMcDonald JColombo AFlunkert SMalnar MVidatic LKuhn PHHutter-Paier BLichtenthaler SFCausevic MDominko KPigoni MKrainc DGunnersen JMTahirovic SfalseBACE1-cleavage of Sez6 and Sez6L is elevated in Niemann-Pick type C disease mouse brains.It is intriguing that a rare, inherited lysosomal storage disorder Niemann-Pick type C (NPC) shares similarities with Alzheimer's disease (AD). We have previously reported an enhanced processing of β-amyloid precursor protein (APP) by β-secretase (BACE1), a key enzyme in the pathogenesis of AD, in NPC1-null cells. In this work, we characterized regional and temporal expression and processing of the recently identified BACE1 substrates seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), and APP, in NPC1-/- (NPC1) and NPC1+/+ (wt) mouse brains. We analysed 4-weeks old brains to detect the earliest changes associated with NPC, and 10-weeks of age to identify changes at terminal disease stage. Sez6 and Sez6L were selected due to their predominant cleavage by BACE1, and their potential2018-01-01T00:00:00Z20182025-04-18T17:31:21.864Z2019-03-26T23:46:54ZS-EPMC60348742997978910.1371/journal.pone.0200344