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Common Genetic Variants of the Mitochondrial Trafficking System and Mitochondrial Uncoupling Proteins Affect the Development of Two Slowly Developing Demyelinating Disorders, Leukoaraiosis and Multiple Sclerosis

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Abstract:

As the central energy source, the mitochondria are of great importance in the maintenance of the glia cells of the brain. It is presumed that mitochondrial energy production is affected not only by wellndash characterized genetic mutations of the mitochondria, which are associated with severe malfunctions and resultant acute glia and neuronal cell death, but also by a number of other unfavorable genetic variants. The genetic variants of the kinesin motor proteins and mitochondrial uncoupling proteins (UCPs) are believed to influence the mitochondrial energy production in different distress states of the glia cells. The kinesin motor proteins carry the mitochondria from the central parts to the peripheral parts of the glia cells, where myelin protein synthesis takes place. The UCPs are essential for regulation of the mitochondrial membrane potential under different physiological conditions, thereby finally attuning mitochondrial energy production in environmental states such as cold exposure, fasting or chronic mild hypoxia. While the capacity of the kinesin motor proteins can affect the number of mitochondria in the peripheral parts of the glia cells, the functional features of the UCPs can affect the degree of energy production of the mitochondria by influencing the mitochondrial membrane potential. The different genetic variants may display different activities, and some may result in a slowly developing energy shortage in the glia cells. In this context, this article discusses the roles of genetic variants of the kinesin motor proteins and UCPs in slowly developing diseases of the white matter of the brain as multiple sclerosis and leukoaraiosis.

Keywords: Genetic variants; Hypertension; Kinesin motor proteins; Leukoaraiosis; MITOCHONDRIA; Multiple sclerosis; UCPs; genetic alterations; genetic mutations; genetic variants; glia cells; leukoaraiosis; multiple sclerosis; uncoupling proteins

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710792927868

Affiliations: Department of Neurology and Cerebrovascular Diseases, Pandy County Hospital, Gyula, H-5600 Bekescsaba, Pipacs koz 9, Hungary.

Publication date: October 1, 2010

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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