UCL Queen Square Institute of Neurology


Parkinson's-linked mutation makes neurons vulnerable to calcium-induced death

13 March 2009

A new study reveals the mechanism by which a genetic mutation linked with Parkinson's disease (PD) renders dopamine neurons particularly vulnerable to cell injury and death. The research is published by Cell Press in the March 13th issue of the journal Molecular Cell. PD is a neurodegenerative disease characterized by a specific loss of dopamine neurons. Several genes have been linked with inherited forms of PD. Many of these genes encode proteins that are targeted to mitochondria, tiny intracellular "power plants" that metabolize oxygen and generate energy. Mitochondria also play a major role in maintaining appropriate calcium levels inside of cells. Abnormal calcium levels can be toxic to neurons and are associated with a range of neurodegenerative diseases.

Mutations in the PINK1 gene cause an inherited form of PD and research has shown that PINK1 is localized to mitochondria. "We previously demonstrated that PINK1 deficiency results in an age related loss of neuronal viability, and an increased sensitivity to mitochondrial dysfunction. However, the mechanisms underlying this mitochondrial pathophysiology remained unknown," explains senior study author Dr. Andrey Y. Abramov from the Institute of Neurology in London (Department of Molecular Neuroscience)

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reference >> PINK1-Associated Parkinson's Disease Is Caused by Neuronal Vulnerability to Calcium-Induced Cell Death.
Sonia Gandhi, Alison Wood-Kaczmar, Zhi Yao, Helene Plun-Favreau, Emma Deas, Kristina Klupsch, Julian Downward, David S. Latchman, Sarah J. Tabrizi, Nicholas W. Wood, Michael R. Duchen and Andrey Y. Abramov
Molecular Cell, Volume 33, Issue 5, 627-638, 13 March 2009. doi:10.1016/j.molcel.2009.02.013