Conclusions
The results provide in vivo evidence for CMA plays a pivotal role in METH-induced neurotoxicity, and upregulation of Hsc70 expression significantly protects neuronal cells against METH-induced toxicity. This research may pave the way for potential therapeutic approaches targeting CMA for METH abuse and neurodegenerative disorders.
Methods
We detected changes in the chaperone protein Hsc70 and the lysosomal surface receptor Lamp-2a after METH treatment and then regulated these two proteins by small interfering RNA and DNA plasmid transfection to investigate how CMA influences METH-induced neurotoxicity.
Results
We found that CMA activity is decreased after METH exposure in neurons and downregulated Lamp-2a can aggravate the neurotoxicity induced by α-Syn after METH exposure and that Hsc70 overexpression can relieve the abnormal levels of alpha-synuclein and its aggregate forms and the increase in cell apoptosis induced by METH. Conclusions: The results provide in vivo evidence for CMA plays a pivotal role in METH-induced neurotoxicity, and upregulation of Hsc70 expression significantly protects neuronal cells against METH-induced toxicity. This research may pave the way for potential therapeutic approaches targeting CMA for METH abuse and neurodegenerative disorders.