Pathological Protein Targets in Parkinson's Disease: Progress Towards the Development of Disease-Modifying Therapies - PubMed
4 days ago
- #Parkinson's Disease
- #Neurodegenerative Disorders
- #Disease-Modifying Therapies
- Parkinson's disease (PD) lacks disease-modifying therapies despite being a common neurodegenerative disorder.
- Recent genetic research has identified key pathological protein targets: alpha-synuclein, LRRK2, and GCase, linked to lysosomal dysfunction and PD pathology.
- Immunotherapy and small molecule approaches are being developed to target aggregated alpha-synuclein to halt disease progression.
- LRRK2 kinase inhibitors are in late-phase clinical trials to counteract the enzyme's overactivity caused by pathogenic mutations.
- GCase-targeted therapies, including small molecule chaperones and activators, aim to restore impaired lysosomal activity due to PD-associated mutations.
- Phase I trials show these therapies are generally tolerated, but challenges remain in advancing to phase II and beyond.