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Using physiologically relevant iPSC-derived dopaminergic neurons (DAns) from PD patients carrying the A53T SNCA or the SNCA Tripl mutation this work addressed the cellular mechanisms associated with α synuclein in PD pathology. Detailed cell biological and transciptomics work revealed perturbations in the expression of genes linked to mitochondrial function together with increased endoplasmic reticulum stress and impairments in cholesterol and lipid homeostasis. This paper suggests that α Syn cellular pathology impacts cellular bioenergetics in dopamine neurons which may be the cause of cytotoxicity leading to cell loss of DAns in PD.

Original publication

DOI

10.1093/hmg/ddz038

Type

Journal article

Publication Date

11/02/2019

Addresses

https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddz038/5315478

Keywords

diabetic autonomic neuropathy , respiration , parkinson disease , mutation , mitochondria , danazol , lipids , pathology , stress , alpha-synuclein, dopaminergic, neurons , mitochondrial membranes , perturbations