alpha-synuclein and nitazoxanide

Upregulation and aggregation of the pre-synaptic protein, α-synuclein plays a key role in Parkinson's disease (PD) and mitochondrial dysfunction was surmised to be an upstream event in the disease pathogenesis. Emerging reports identified the role of nitazoxanide (NTZ), an anti-helminth drug, in enhancing mitochondrial oxygen consumption rate (OCR) and autophagy. In the present study, we have examined the mitochondrial effects of NTZ in mediating cellular autophagy and subsequent clearance of both endogenous and pre-formed aggregates of α-synuclein in cellular model of PD. Our results demonstrate that the mitochondrial uncoupling effects of NTZ results in the activation of AMPK and JNK, which in-turn leads to the enhancement of cellular autophagy. Also,1-methyl-4-phenylpyridinium (MPP

Topics: alpha-Synuclein; AMP-Activated Protein Kinases; Autophagy; Humans; MAP Kinase Signaling System; Mitochondria; Parkinson Disease