Involvement of polyglutamine endolysis followed by pyroglutamate formation in the pathogenesis of triplet repeat/polyglutamine-expansion diseases.

Abstract:

:The mechanism by which polyglutamine expansions in several proteins lead to neurodegenerative disorders remains largely unknown. The biochemical properties of polyglutamine repeats suggest one possible explanation; endolytic cleavage at a glutaminyl-glutaminyl bond followed by pyroglutamate formation may contribute to the pathogenesis through augmenting the catabolic stability, hydrophobicity, amyloidogenicity, and neurotoxicity of the polyglutaminyl proteins. The hypothesis points out novel therapeutic strategies to delay disease onset in genetically diagnosed presymptomatic patients.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

Saido TC

doi

10.1054/mehy.1999.0866

keywords:

subject

Has Abstract

pub_date

2000-03-01 00:00:00

pages

427-9

issue

3

eissn

0306-9877

issn

1532-2777

pii

S0306-9877(99)90866-6

journal_volume

54

pub_type

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