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.

Polyglutamine expansions in proteins contribute to neurodegenerative disorders by enhancing their catabolic stability, hydrophobicity, amyloidogenicity, and neurotoxicity.

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

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