کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1902469 1045749 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Wnt signaling in Alzheimer's disease: Up or down, that is the question
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Wnt signaling in Alzheimer's disease: Up or down, that is the question
چکیده انگلیسی

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, neuropathologically characterized by amyloid-β (Aβ) plaques and hyperphosphorylated tau accumulation. AD occurs sporadically (SAD), or is caused by hereditary missense mutations in the amyloid precursor protein (APP) or presenilin-1 and -2 (PSEN1 and PSEN2) genes, leading to early-onset familial AD (FAD). Accumulating evidence points towards a role for altered Wnt/β-catenin-dependent signaling in the etiology of both forms of AD. Presenilins are involved in modulating β-catenin stability; therefore FAD-linked PSEN-mediated effects can deregulate the Wnt pathway. Genetic variations in the low-density lipoprotein receptor-related protein 6 and apolipoprotein E in AD have been associated with reduced Wnt signaling. In addition, tau phosphorylation is mediated by glycogen synthase kinase-3 (GSK-3), a key antagonist of the Wnt pathway.In this review, we discuss Wnt/β-catenin signaling in both SAD and FAD, and recapitulate which of its aberrant functions may be critical for (F)AD pathogenesis. We discuss the intriguing possibility that Aβ toxicity may downregulate the Wnt/β-catenin pathway, thereby upregulating GSK-3 and consequent tau hyperphosphorylation, linking Aβ and tangle pathology. The currently available evidence implies that disruption of tightly regulated Wnt signaling may constitute a key pathological event in AD. In this context, drug targets aimed at rescuing Wnt signaling may prove to be a constructive therapeutic strategy for AD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Ageing Research Reviews - Volume 8, Issue 2, April 2009, Pages 71–82
نویسندگان
, , ,