What happens if the cell leaves the mitochondria to their fate – new facts about Parkinson's disease

Parkinson's disease is a degenerative disorder characterized by tremor, gait abnormalities and a slowing of physical movement. It is caused by the lack of dopamine produced in the neurons in substantia nigra. The neurons loose their own mitochondria, the organelles that produce energy for cells. This process has devastating effects on the survival of the cells.

Although representing only two per cent of the body weight, the brain uses 20 per cent of its energy consumption. In particular, as it was explained in an article which was published in Science Translational Medicine (Scherzer et al., 2010), researchers from Harvard Medical School, Brigham and Women's Hospital led by Clemens Scherzer identified ten groups of genes, which hadn´t been related to the Parkinson´s disease before. The lack of their expression determines defects in mitochondrial electron transport, the use and detection of cellular levels of glucose.

Previous studies have already linked the disease to defects in mitochondria, but they had not revealed any specific group of genes involved in the pathogenesis. The researchers (Scherzer et al., 2010) analyzed 185 tissue samples from the substantia nigra of patients suffering from this disease and then they analyzed the gene expression in their cells.

Ten groups of genes encoding proteins are responsible for cellular processes linked to mitochondrial function and energy production. The elimination of these genes leads to serious damage to various components of the brain energy metabolism. Particularly affected is the electron transport chain, which is a series of reactions controlled by the mitochondria through five molecular complexes, only one of which had been previously considered to be deficient in Parkinson's disease. But the new research has shown that they are all in varying degrees.

The research also found that the expression of these genes responds to the activation of a gene regulator, PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α), which is NOT expressed in patients suffering from the disease.

"The most exciting result of this study is the discovery that PGC-1alpha can be a new therapeutic target for an early treatment. PGC-1alpha is a switch that activates hundreds of mitochondrial genes, including many of those which are necessary for the preservation and the repair of 'power generation plants' of the mitochondria," said Scherzer. He observed that drugs which work as activators of PGC-1alpha are already available and used in treatment of other diseases. According to him a pharmaceutical research could lead to new drugs which would be able to perform this action in the brain, an organ which, because of the blood-brain barrier, can´t be reached by most of the molecules.

Translated by: Pavla Čermáková

Story source: http://lescienze.espresso.repubblica.it/

Original work: B. Zheng, Z. Liao, J. J. Locascio, K. A. Lesniak, S. S. Roderick, M. L.Watt, A. C. Eklund, Y. Zhang-James, P. D. Kim, M. A. Hauser, E. Grünblatt, L. B. Moran, S. A. Mandel, P. Riederer, R. M. Miller, H. J. Federoff, U. Wüllner, S. Papapetropoulos, M. B. Youdim, I. Cantuti-Castelvetri, A. B. Young, J. M. Vance, R. L. Davis, J. C. Hedreen, C. H. Adler, T. G. Beach, M. B. Graeber, F. A. Middleton, J.-C. Rochet, C. R. Scherzer, the Global PD Gene Expression (GPEX) Consortium, PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.. Sci. Transl. Med. 2, 52ra73 (2010)

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