Scientific Reports (Jul 2024)

High frequency electrical stimulation reduces α-synuclein levels and α-synuclein-mediated autophagy dysfunction

  • Jimmy George,
  • Kashfia Shafiq,
  • Minesh Kapadia,
  • Lorraine V. Kalia,
  • Suneil K. Kalia

DOI
https://doi.org/10.1038/s41598-024-64131-3
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 17

Abstract

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Abstract Accumulation of α-synuclein (α-Syn) has been implicated in proteasome and autophagy dysfunction in Parkinson’s disease (PD). High frequency electrical stimulation (HFS) mimicking clinical parameters used for deep brain stimulation (DBS) in vitro or DBS in vivo in preclinical models of PD have been found to reduce levels of α-Syn and, in certain cases, provide possible neuroprotection. However, the mechanisms by which this reduction in α-Syn improves cellular dysfunction associated with α-Syn accumulation remains elusive. Using HFS parameters that recapitulate DBS in vitro, we found that HFS led to a reduction of mutant α-Syn and thereby limited proteasome and autophagy impairments due to α-Syn. Additionally, we observed that HFS modulates via the ATP6V0C subunit of V-ATPase and mitigates α-Syn mediated autophagic dysfunction. This study highlights a role for autophagy in reduction of α-Syn due to HFS which may prove to be a viable approach to decrease pathological protein accumulation in neurodegeneration.

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