Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts.
作者： Youssef M. Mousa , Ihab M. Abdallah , Misako Hwang , Douglas R. Martin , Amal Kaddoumi
DOI: 10.1038/S41598-020-60664-5
关键词: Microglia 、 Amylin 、 Pathogenesis 、 Cerebral amyloid angiopathy 、 Lipid raft 、 Endocrinology 、 Pramlintide 、 Ganglioside 、 Amyloid precursor protein 、 Internal medicine 、 Chemistry
摘要: A major characteristic of Alzheimer’s disease (AD) is the accumulation misfolded amyloid-β (Aβ) peptide. Several studies linked AD with type 2 diabetes due to similarities between Aβ and human amylin. This study investigates effect amylin pramlintide on pathogenesis predisposing molecular mechanism(s) behind observed effects in TgSwDI mouse, a cerebral amyloid angiopathy (CAA) model. Our findings showed that thirty days intraperitoneal injection or increased burden mice brains. Mechanistic revealed both peptides altered amyloidogenic pathway production by modulating precursor protein (APP) γ-secretase levels lipid rafts. In addition, B4GALNT1 enzyme GM1 ganglioside, only level GM2 ganglioside. Increased gangliosides play an important role regulating proteins brain was associated synaptic loss, apoptosis, microglia activation. conclusion, our increase related pathology brains, suggest therapeutic use could risk AD.
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