M H R Ludtmann
Mitochondrial calcium imbalance in Parkinson's disease
Ludtmann, M H R; Abramov, A Y
Authors
A Y Abramov
Abstract
Multiple factors are involved in the mechanism(s) of neuronal loss in neurodegenerative disorders whilst mitochondria are thought to play a central role in neurodegeneration of Parkinson’s disease. Mitochondria are vital to cellular functions by supplying energy in form of ATP and affect cell physiology via calcium, ROS and signalling proteins. Changes in mitochondrial calcium homeostasis and ROS overproduction can induce cell death by triggering mitochondrial permeability transition pore opening. One of the major triggers for PTP is mitochondrial calcium overload. Mitochondrial Ca2+ homeostasis is regulated by electrogenic calcium uptake (via Ca2+ uniporter MCU) and efflux (in excitable cells via Na+/Ca2+ exchanger NCLX). NCLX inhibition has been described in a familial form of Parkinson’s disease where PINK-1 deficiency leads to a delayed calcium efflux and mitochondrial Ca2+ overload in response to physiological Ca2+ stimulation. Overexpression of NCLX in PINK-1 deficient neurons not only protects against mitochondrial calcium overload and calcium induced cell death but also restores mitochondrial bioenergetics in these neurons. Mitochondrial NCLX might therefore play an important role in the mechanism(s) of neurodegeneration in a variety of neurodegenerative disorders and activation of this exchanger may offer a novel therapeutic target.
Citation
Ludtmann, M. H. R., & Abramov, A. Y. (2018). Mitochondrial calcium imbalance in Parkinson's disease. Neuroscience Letters, 663, 8690. https://doi.org/10.1016/j.neulet.2017.08.044
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 16, 2017 |
Publication Date | Jan 10, 2018 |
Deposit Date | Jun 28, 2018 |
Journal | Neuroscience Letters |
Print ISSN | 0304-3940 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 663 |
Pages | 8690 |
DOI | https://doi.org/10.1016/j.neulet.2017.08.044 |
Public URL | https://rvc-repository.worktribe.com/output/1389289 |
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