TL;DR
This review focuses on translational insights linking α-syn pathology to dysregulated stress-response and protein quality-control pathways, intending to identify potential targets for disease-modifying intervention.
It is proposed that a systems-level approach can be taken where PD is understood as a disease characterized by the imbalance in proteostasis, and potential treatment modalities include small molecules targeting lysosome function, CMA enhancers, gene therapy, and antibodies against extracellular α-synuclein.
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide, characterized pathologically by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies, which predominantly consist of misfolded α-synuclein (α-Syn) aggregates. Recent advances have highlighted...
In conclusion, small-molecule-based therapies represent a promising multi-targeted strategy for PD; however, key translational challenges and unresolved questions remain, including optimisation of pharmacokinetics, target specificity, and blood-brain barrier penetration and validation in clinical settings.
A model in which the balance between α-syn production and clearance influences disease progression alongside protein misfolding is supported, which provides a quantitative perspective on disease heterogeneity, and highlights therapeutic opportunities aimed at reducing α-syn burden and restoring proteostatic balance.
This integrated framework reframes PD as a disorder of impaired cellular maintenance rather than solely a consequence of late-stage degenerative processes, and provides a translational shift from mechanism-based biomarkers to early detection of mitochondrial failure and supports therapeutic strategies aimed at restorin...
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the pathological misfolding and aggregation of α-synuclein (α-syn), which leads to dopaminergic neuronal loss and multisystem dysfunction. Conventional clinical diagnosis is often delayed until after substantial neuronal degeneration...
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