AI Article Synopsis
- The study explores the critical role of the WDFY3/Alfy protein in managing and breaking down toxic huntingtin aggregates linked to Huntington's disease.
- Depleting WDFY3 in mouse models leads to faster accumulation of these aggregates and worsens disease symptoms, highlighting its importance in neuroprotection.
- The research suggests WDFY3 could also serve as a genetic factor influencing not just Huntington’s, but potentially other neurodegenerative diseases and aging processes.
Article Abstract
The role protein aggregates play in the pathogenesis of neurodegenerative diseases has been a question since their initial observation. In this autophagic punctum, we discuss our recent findings of how the selectivity scaffold/adaptor WDFY3/Alfy is required for the turnover of aggregated mutant HTT (huntingtin; mHTT) in the adult brain, and how it confers resistance to Huntington disease (HD)-like symptoms. Depletion of WDFY3 in a mouse model of HD accelerates mHTT accumulation, and this is accompanied by an accelerated onset of motoric and neuropathological phenotypes, indicating that WDFY3 levels and the rate of aggregate accumulation can modify disease pathogenesis. Given that the accelerated accumulation is also recapitulated in medium spiny neurons created via direct conversion from human HD fibroblasts, we propose that WDFY3 is a genetic modifier of HD and suggest that it may also influence aging and the pathogenesis of other neurological disorders.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144867 | PMC |
| http://dx.doi.org/10.1080/15548627.2020.1739448 | DOI Listing |
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