Parkinson-disease-patient-derived cells presented differences in their energetic profile, imbalanced proliferation, apoptosis, mitophagy, and a reduced differentiation efficiency to tyrosine hydroxylase positive (TH+) neurons compared to controls’ cells. Correction of a patient’s point mutation ameliorated the metabolic properties and neuronal firing rates as well as reversing the differentiation phenotype, and reducing the increased astrocytic levels. Treatment with 2-hydroxypropyl-β-cyclodextrin increased the autophagy and mitophagy capacity of neurons concomitant with an improved dopaminergic differentiation of patient-specific neurons in midbrain organoids and ameliorated neurotoxicity in a mouse model.
Javier Jarazo, Kyriaki Barmpa, Jennifer Modamio, Cláudia Saraiva, Sònia Sabaté-Soler, Isabel Rosety, Anne Griesbeck et al. (2022) Parkinson’s Disease Phenotypes in Patient Neuronal Cultures and Brain Organoids Improved by 2-Hydroxypropyl-β-Cyclodextrin Treatment. Movement Disorders 37, 80-94.
First published: 12 October 2021 https://doi.org/10.1002/mds.28810
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