Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and Prion diseases, are characterized by the formation and propagation of misfolded protein conformers and progressive neuronal cell death. Although the causal relationship between protein misfolding and neurodegeneration is unambiguous, the underlying mechanisms triggering protein misfolding and neuronal dysfunction.
Notably, the majority of neurodegenerative diseases are not associated with mutations in the aggregation-prone proteins, indicating that post-translational processes and the cellular environment play a key role. In the lecture, I will specifically discuss the role of liquid-liquid phase separation and cellular membranes in triggering or preventing a conformational transition of physiological folded proteins into neurotoxic aggregates.