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

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.

Automated summary

Current research accepts the theory that pathological proteins associated with neurodegenerative disorders behave similarly to prions. Protein misfolding and prion-like properties play significant roles in neurodegenerative disorders, influencing disease progression and potential therapeutic strategies.