Virtues and woes of AChE alternative splicing in stress-related neuropathologies

Eran Meshorer*, Hermona Soreq

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

169 Scopus citations

Abstract

The ACh hydrolyzing enzyme acetylcholinesterase (AChE) is a combinatorial series of proteins with variant N and C termini generated from alternate promoter usage and 3′ alternative splicing. Neuronal AChE variants show indistinguishable enzymatic activity yet differ in their expression, multimeric assembly and membrane-association patterns. Differentially induced under stress, they show distinct non-hydrolytic properties and interact with different protein partners. Recent findings suggest that transcriptional and post-transcriptional regulation of AChE pre-mRNA is a neuroprotection strategy but might involve long-term damage. Specifically, variant-specific causal involvement of AChE in the progression of both neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) and neuromuscular syndromes (e.g. myasthenia gravis) raises the possibility that future therapeutic drugs might target specific AChE variant(s) or the corresponding RNA transcripts.

Original languageAmerican English
Pages (from-to)216-224
Number of pages9
JournalTrends in Neurosciences
Volume29
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Bibliographical note

Funding Information:
Our work is supported by the Israel Science Foundation 618-02-1, the European Community LSHM-CT-2003–503330 and European Alternative Splicing Network of Excellence- LSH-2004-1.1.5-3, the German–Israeli-Foundation (Grant 673), and Ester Neuroscience.

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