Here, the authors generated dopamine neurons from induced pluripotent stem cells derived from people with young-onset Parkinson disease (YOPD). Nearly all the neuronal lines exhibited accumulated α-synuclein, widely implicated in PD, and phosphorylated PKCα (pPKCα). Treatment of these cells with PEP005, a PKC agonist that can promote the lysosomal pathway, reduced α-synuclein and pPKCα levels, but its effect on the former was surprisingly via activation of proteasomal degradation. Thus, elevated pPKCα may be a molecular YOPD phenotype and PEP005 may be a therapeutic candidate.
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Laperle, A. H. et al. iPSC modeling of young-onset Parkinson’s disease reveals a molecular signature of disease and novel therapeutic candidates. Nat. Med. https://doi.org/10.1038/s41591-019-0739-1 (2020)
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Yates, D. Modelling Parkinson disease. Nat Rev Neurosci 21, 120 (2020). https://doi.org/10.1038/s41583-020-0273-7
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DOI: https://doi.org/10.1038/s41583-020-0273-7
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