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Medicine and Health Sciences

Theses and Dissertations

2024

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Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis Feb 2024

Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis

Theses and Dissertations

The ability of glia to tightly regulate neuronal health and homeostasis in the CNS is conserved across species. Yet, despite the ability to degrade protein aggregates, glia are vulnerable to the accumulation of neurotoxic amyloid aggregates during neurodegenerative disease progress, and even exacerbate their spread. A developing narrative highlights glia as a double-edged sword in neurodegenerative diseases: initially capable of dynamically responding to amyloid aggregate-ladened dying neurons but also capable of inducing chronic inflammation and creating seeding-competent amyloid oligomers. Thus, uncovering the mechanisms that allow glia to control aggregate deposition while preventing the neurotoxic effects and seed generation is vital …