Prion-like properties of the mutant huntingtin protein in living organisms: the evidence and the relevance.

TitlePrion-like properties of the mutant huntingtin protein in living organisms: the evidence and the relevance.
Publication TypeJournal Article
Year of Publication2022
AuthorsAlpaugh, M, Denis, HL, Cicchetti, F
JournalMol Psychiatry
Volume27
Issue1
Pagination269-280
Date Published2022 Jan
ISSN1476-5578
Abstract

If theories postulating that pathological proteins associated with neurodegenerative disorders behave similarly to prions were initially viewed with reluctance, it is now well-accepted that this occurs in several disease contexts. Notably, it has been reported that protein misfolding and subsequent prion-like properties can actively participate in neurodegenerative disorders. While this has been demonstrated in multiple cellular and animal model systems related to Alzheimer's and Parkinson's diseases, the prion-like properties of the mutant huntingtin protein (mHTT), associated with Huntington's disease (HD), have only recently been considered to play a role in this pathology, a concept our research group has contributed to extensively. In this review, we summarize the last few years of in vivo research in the field and speculate on the relationship between prion-like events and human HD. By interpreting observations primarily collected in in vivo models, our discussion will aim to discriminate which experimental factors contribute to the most efficient types of prion-like activities of mHTT and which routes of propagation may be more relevant to the human condition. A look back at nearly a decade of experimentation will inform future research and whether therapeutic strategies may emerge from this new knowledge.

DOI10.1038/s41380-021-01350-4
Alternate JournalMol Psychiatry
PubMed ID34711942
Grant List28941 / / Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec) /
PJT-168865 and PJT-162164 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /