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Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication
Problems with cell recycling in nerve cells and midbrain models made from stem cells with extra copies of the SNCA gene
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Abstract
In 3xSNCA neuronal cultures, early autophagy defects were detected.
- In human midbrain organoids derived from induced pluripotent stem cells of Parkinson's disease patients, reduced autolysosome area was observed.
- Total and phosphorylated α-Synuclein levels increased in these organoids by day 50 of differentiation.
- Decreased electrophysiological activity was noted at the same time point.
- By day 70 of differentiation, autophagy impairment was more pronounced, coinciding with dopaminergic neuron dysfunction.
- These findings reveal a potential link between impaired autophagy, α-Synuclein accumulation, and neuronal degeneration in Parkinson's disease.
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