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Glutamatergic synaptic resilience to overexpressed human alpha-synuclein
Patrícia I Santos1, Inés Hojas García-Plaza2, Ali Shaib3
1Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
NPJ Parkinson'S Disease
|August 12, 2025
Summary
Overexpressing alpha synuclein (aSyn) in rodent neurons did not impair presynaptic function or cause toxicity. These findings suggest that aSyn neurotoxicity in Parkinson's disease (PD) may not be solely due to overexpression alone.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alpha synuclein (aSyn) is a key protein implicated in Parkinson's disease (PD).
- Genetic factors, including SNCA gene triplications, lead to increased aSyn levels in familial PD.
- The direct impact of elevated aSyn on presynaptic function remains incompletely understood.
Purpose of the Study:
- To investigate whether overexpression of human alpha synuclein (haSyn) alone impairs presynaptic function in rodent glutamatergic neurons.
- To determine if haSyn levels mimicking familial PD genetic alterations induce neurotoxicity.
Main Methods:
- Overexpression of haSyn in rodent glutamatergic neurons.
- Analysis of presynaptic and postsynaptic protein levels (SNAP-25, PSD-95).
- Electrophysiological recordings in autaptic cultures to assess neurotransmission and plasticity.
Main Results:
- haSyn overexpression did not induce toxicity in cultured neurons.
- No significant changes were observed in SNAP-25 or PSD-95 levels.
- Evoked and spontaneous neurotransmission, as well as synaptic plasticity, remained unaffected.
Conclusions:
- Rodent glutamatergic neurons exhibit resilience to alpha synuclein overexpression.
- The neurotoxic effects of aSyn may depend on factors beyond mere overexpression.
- Further research is needed to elucidate the complex biology and pathobiology of aSyn in Parkinson's disease.
