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N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models - PubMed

5 hours ago
  • #N-acetyl-l-leucine
  • #Parkinson's disease
  • #synaptic function
  • N-acetyl-l-leucine (NALL) reduces phosphorylated α-synuclein (pS129-syn) levels in Parkinson's disease (PD) models.
  • NALL upregulates lysosomal, mitochondrial, and synaptic proteins without causing cytotoxicity.
  • The reduction of pS129-syn by NALL depends on the serine protease HTRA1.
  • NALL increases wild-type parkin expression, improving synaptic function in dopaminergic neurons.
  • In LRRK2R1441C knockin mice, NALL decreases pS129-syn, elevates parkin levels, and improves motor learning deficits.
  • NALL shows therapeutic potential for PD by targeting α-synuclein pathology and synaptic dysfunction.