Convergent molecular pathways to inherited Parkinson's disease - PubMed
a day ago
- #LRRK2
- #Parkinson's disease
- #GBA1
- Pathogenic LRRK2 variants increase kinase activity, while GBA1 variants reduce lysosomal glucocerebrosidase activity, both linked to Parkinson's disease.
- LRRK2 phosphorylates Rab GTPases, influencing cellular pathology through phosphorylation-specific effectors.
- LRRK2 roles include promoting exocytosis of lysosome-related organelles and regulating primary cilia formation in neurons and astrocytes.
- Loss of primary cilia or GBA1 deficiency impairs Hedgehog signaling, reducing neuroprotective factors for dopamine neurons.
- LRRK2 inhibitors in mutant mice restore cilia and neuroprotective factor production, showing therapeutic potential.