Impairment of proteasome and anti-oxidative pathways in the induced pluripotent stem cell model for sporadic Parkinson's disease

Parkinsonism & Related Disorders
Kuo-Hsuan ChangChiung-Mei Chen

Abstract

Parkinson's disease (PD) is associated with the progressive degeneration of dopaminergic neurons with abnormal accumulation of α-synuclein mainly in the ventral midbrain. However, the lack of live human neurons from PD patients and their heterogeneous pathogenic nature limit mechanistic studies and therefore the development of drugs to modify the disease progression of PD. The evolution of induced pluripotent stem cell (iPSC) technology makes it possible to generate patient-specific neurons to explore the pathogenesis in individual PD patients. We generated PD-iPSCs from a sporadic early onset PD patient carrying a heterozygous deletion of exon 5 (Ex5del) in PARK2. The expression of α-synuclein and proteasome and anti-oxidative functions were examined in differentiated iPSC-derived neurons. The neurons derived from our PD-iPSCs demonstrated abnormal α-synuclein accumulation and down-regulation of the proteasome and anti-oxidative pathways. Environmental triggers such as proteasome inhibitor MG132 and H2O2 markedly induced cell death, while the proteasome enhancer benzamil and anti-oxidative compound genipin significantly rescued these increased susceptibilities. These results demonstrate that unique genetic-environmental intera...Continue Reading

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Citations

Nov 2, 2016·Journal of Parkinson's Disease·Eduard BenteaAnn Massie
Apr 12, 2017·Stem Cells and Development·Karin LauschkeVanessa Jane Hall
Sep 13, 2017·Journal of Sports Sciences·Michael F AlmeidaMerari F R Ferrari
Dec 14, 2017·Cell and Tissue Research·Melanie M CobbSteven Finkbeiner
Nov 9, 2018·The European Journal of Neuroscience·Anindita Bose, M Flint Beal
Jan 19, 2019·The European Journal of Neuroscience·Beatrice WeykopfOliver Brüstle
Sep 22, 2018·Molecular Neurobiology·Kuo-Hsuan ChangChiung-Mei Chen
Jul 12, 2020·Antioxidants·Kuo-Hsuan Chang, Chiung-Mei Chen
Oct 19, 2019·Stem Cell Research & Therapy·Shih-Hsuan MaoChien-Tzung Chen
Feb 16, 2020·Acta Neuropathologica Communications·Chris McKinnonSuneil K Kalia
May 1, 2020·NPJ Parkinson's Disease·Jenne TranCedric Bardy
Nov 20, 2020·Cellular and Molecular Life Sciences : CMLS·Meritxell Pons-EspinalAntonella Consiglio
Feb 13, 2021·NPJ Parkinson's Disease·Jenne TranCedric Bardy
Apr 4, 2021·Brain Sciences·Sahar AvazzadehLeo R Quinlan
Nov 21, 2021·Molecular and Cellular Neurosciences·Angel J Santiago-LopezClaire-Anne N Gutekunst

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