FEBS Journal, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 25, 2025
A possible consequence of the process protein aggregation in neurodegenerative diseases is depletion soluble species (proteinopenia), which may, at least some cases, reduce function/activity. This concept, often overlooked, may play a role synucleinopathies such as Parkinson's disease (PD), and dementia with Lewy bodies (DLB), where α‐synuclein (aSyn) known to accumulate insoluble inclusions. aSyn crossroads between cellular proteostasis lipidostasis networks and, therefore, we must be aware complexity face when try understand molecular basis synucleinopathies. Importantly, β‐glucocerebrosidase (GCase), sphingolipid hydrolase also strongly implicated PD DLB, are connected lipid biology quality control function. Thus, changes normal relationship these two proteins shift balance cell lead proteinopathy and/or proteinopenia, while affecting cells brain. pathological mechanisms that (a) loss‐of‐function, (b) gain‐of‐toxic function, (c) alterations need carefully analyzed integrated our study underpinnings mechanisms. Here, highlight implications form aSyn, GCase, discuss how state‐of‐the‐art ‘omics technologies’ could deployed assist clinical assessment
Language: Английский