Duncan NRI Faculty and Staff Publications

Language

English

Publication Date

1-5-2026

Journal

Journal of Experimental Medicine

DOI

10.1084/jem.20241336

PMID

41128726

Abstract

Polyglutamine (polyQ) diseases, caused by a CAG repeat expansion encoding a glutamine tract in nine distinct proteins, present a complex molecular puzzle in which each piece contributes to neurodegeneration. While each of the causative proteins has a distinct function, the downstream consequences of polyQ toxicity are often similar, including protein accumulation, transcriptional dysregulation, somatic CAG repeat instability, disrupted energy homeostasis, compromised synaptic function, and selective neuronal death. This review summarizes emerging insights into how proteins with an expanded polyQ tract disrupt distinct cellular functions, and we examine a multitude of discoveries that are inspiring and reshaping novel therapeutic strategies.

Keywords

Humans, Peptides, Animals, Trinucleotide Repeat Expansion, Neurodegenerative Diseases

Published Open-Access

yes

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