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Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation - PubMed

4 hours ago
  • #LRRK2
  • #alpha-synuclein
  • #autophagy
  • Knockout of phosphatase PPM1H disrupts autophagosome transport in axons.
  • This disruption leads to impaired degradation of axonal alpha-synuclein.
  • Defective autophagy correlates with increased alpha-synuclein aggregation.
  • The effect is dependent on LRRK2 kinase activity and gene-dose-related.
  • LRRK2-RAB axis is identified as a key driver in Parkinson's disease pathophysiology.