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High frequency electrical stimulation reduces α-synuclein levels and α-synuclein-mediated autophagy dysfunction
Jimmy George1, Kashfia Shafiq1, Minesh Kapadia1
1Toronto Western Hospital, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada.
Scientific Reports
|July 12, 2024
Summary
High frequency electrical stimulation (HFS) reduces alpha-synuclein (α-Syn) buildup in Parkinson's disease models. This neuroprotective approach improves autophagy and proteasome function, offering a potential therapy for neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alpha-synuclein (α-Syn) accumulation is linked to cellular dysfunction in Parkinson's disease (PD).
- Proteasome and autophagy pathways are impaired by α-Syn buildup.
- High frequency electrical stimulation (HFS) shows potential for reducing α-Syn and neuroprotection in PD models.
Purpose of the Study:
- To investigate the mechanisms by which HFS reduces α-Syn levels and alleviates cellular dysfunction in PD.
- To explore the role of autophagy in HFS-mediated α-Syn reduction.
- To identify specific molecular targets of HFS in mitigating α-Syn pathology.
Main Methods:
- Utilized in vitro models with HFS parameters mimicking deep brain stimulation (DBS).
- Quantified α-Syn levels and assessed proteasome and autophagy function.
- Investigated the involvement of the V-ATPase ATP6V0C subunit.
Main Results:
- HFS significantly reduced levels of mutant α-Syn.
- HFS ameliorated proteasome and autophagy impairments caused by α-Syn.
- HFS was found to modulate the V-ATPase ATP6V0C subunit, mitigating autophagic dysfunction.
Conclusions:
- HFS effectively reduces pathological α-Syn accumulation in a cellular model of PD.
- Autophagy plays a crucial role in the α-Syn-lowering effects of HFS.
- HFS targeting V-ATPase ATP6V0C presents a promising therapeutic strategy for neurodegenerative diseases characterized by protein aggregation.
