Proteasomal Degradation of Mutant Huntingtin Exon1 Regulates Autophagy.

ABSTRACT: Accumulation of misfolded proteins is implicated in neurodegenerative diseases. One of these is Huntington's disease, which is caused by an expansion of trinucleotide (CAG) repeats in exon 1 of huntingtin gene (HTT). This expansion results in the production of mutant huntingtin exon1 protein (mHttEx1) containing polyglutamine tracks that is prone to cytotoxic aggregation. These mHttEx1 aggregates range from small soluble aggregates to large insoluble inclusion bodies. The mechanisms to clear mHttEx1 aggregates include ubiquitin-dependent proteasomal degradation and autophagy. For the proteasomal degradation of mHttEx1, ubiquitinated protein is first recognized by the Cdc48 complex for extraction and unfolding. For autophagy, mHttEx1 inclusion bodies are engulfed by an autophagosome,

SUBMITTER: Folger A 

PROVIDER: S-EPMC12785617 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature