Dysregulation of astrocytic DNAJC6 contributes to sporadic Parkinson's disease pathogenesis - PubMed
6 hours ago
- #Parkinson's Disease
- #DNAJC6
- #Astrocytes
- DNAJC6 mutations cause juvenile-onset familial Parkinson's disease (PD).
- DNAJC6 expression is downregulated in sporadic PD brains and stem cell models.
- Downregulation involves transcriptional factors NURR1/FOXA2 and LRRK2-mediated stability.
- DNAJC6 is also expressed in astrocytes and reduced in sporadic PD.
- Loss in astrocytes impairs cellular functions and increases inflammation, worsening neurodegeneration.
- Restoring DNAJC6 via CRISPRa in a PD mouse model improved symptoms and pathology.
- Targeting DNAJC6 in neurons and astrocytes may be a therapeutic strategy for sporadic PD.