N-acetylcholinesterase-induced apoptosis in Alzheimer's disease.

ABSTRACT:

Background

Alzheimer's disease (AD) involves loss of cholinergic neurons and Tau protein hyper-phosphorylation. Here, we report that overexpression of an N-terminally extended "synaptic" acetylcholinesterase variant, N-AChE-S is causally involved in both these phenomena.

Methodology and principal findings

In transfected primary brain cultures, N-AChE-S induced cell death, morphological impairments and caspase 3 activation. Rapid internalization of fluorescently labeled fasciculin-2 to N-AChE-S transfected cells indicated membranal localization. In cultured cell lines, N-AChE-S transfection activated the Tau kinase GSK3, induced Tau hyper-phosphorylation and caused apoptosis. N-AChE-S-induced cell death was suppressible by inhibiting GSK3 or caspases, by enforced overexpressi

SUBMITTER: Toiber D 

PROVIDER: S-EPMC2518620 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature