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Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
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Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
Gessica Sala1, Tommaso Bocci2, Valentina Borzì3
1Laboratory of Neurobiology, NeuroMI - Milan Center for Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, 48, 20900, Monza, MB, Italy. gessica.sala@unimib.it.
Scientific Reports
|January 27, 2021
Summary
Transcranial Direct Current Stimulation (tDCS) impacts alpha-synuclein (asyn) levels and aggregation in Parkinson's disease models. This study reveals tDCS enhances asyn degradation, suggesting a novel neuroprotective mechanism.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Parkinson's disease is characterized by alpha-synuclein (asyn) aggregation.
- Transcranial Direct Current Stimulation (tDCS) is explored for symptomatic relief in Parkinson's disease.
- The molecular mechanisms and disease-modifying potential of tDCS remain largely unknown.
Purpose of the Study:
- To investigate the effects of tDCS on asyn expression, aggregation, and degradation.
- To elucidate the on-line and off-line molecular mechanisms of tDCS in a cellular model.
- To explore the potential neuroprotective role of tDCS in Parkinson's disease pathology.
Main Methods:
- Utilized a human neuroblastoma cell line.
- Assessed asyn gene and protein expression using real-time PCR and Western blot.
- Measured extracellular asyn levels via Dot blot.
- Induced increased asyn levels using rotenone and lysosomal inhibition.
Main Results:
- tDCS modulated asyn forms, increasing monomeric and decreasing oligomeric species under basal conditions.
- tDCS potentiated asyn degradation, counteracting rotenone-induced accumulation without affecting gene transcription.
- tDCS reduced intracellular and extracellular asyn levels, even independent of autophagic degradation, suggesting additional pathways.
Conclusions:
- tDCS influences asyn expression, aggregation, and degradation through both immediate and delayed effects.
- The findings suggest a potential neuroprotective role for tDCS in Parkinson's disease.
- tDCS may offer a disease-modifying therapeutic strategy beyond symptomatic treatment.

