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A new role for α-synuclein in Parkinson’s disease: Alteration of ER-mitochondrial communication.
Mov Disord. 2015 Jul;30(8):1026-33. doi: 10.1002/mds.26239
Guardia-Laguarta C, Area-Gomez E, Schon EA, Przedborski S
Abstract:
.....We recently showed that wild-type α-synuclein is not present in mitochondria, as previously thought, but rather is located in mitochondrial-associated endoplasmic reticulum membranes. Remarkably, we also found that PD-related mutated α-synuclein results in its reduced association with mitochondria-associated membranes, coincident with a lower degree of apposition of endoplasmic reticulum with mitochondria and an increase in mitochondrial fragmentation, as compared with wild-type. This new subcellular localization of α-synuclein raises fundamental questions regarding the relationship of α-synuclein to mitochondria-associated membranes function, in both normal and pathological states. In this article, we attempt to relate aspects of PD pathogenesis to what is known about mitochondria-associated membranes' behavior and function. We hypothesize that early events occurring in dopaminergic neurons at the level of the mitochondria-associated membranes could cause long-term disturbances that lead to PD.
PMID: 25952565
Tags: alpha-synuclein, membranes, mitochondria, parkinson's