Mitochondrial changes associated with demyelination: Consequences for axonal integrity

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• 作者：Graham R. Campbell^a ; Don J. Mahad^a ; ^b ; ^c ; ^{d.j.mahad@ncl.ac.uk}
• 关键词：尾-APP ; beta-amyloid precursor protein ; CNS ; central nervous system ; KSS ; Kearns&ndash ; Sayre syndrome ; LHON ; Leber's hereditary optic neuritis ; MELAS ; mitochondrial encephalopathy ; lactic acidosis and stroke-like episodes ; MERRF ; myoclonic epilepsy with r
• 刊名：Mitochondrion
• 出版年：2012
• 期刊代码：39_15677249
• 类别：neu
• 出版时间：March, 2012
• 卷：12
• 期：2
• 页码：173-179
• 文件大小：562 K

摘要

The loss of myelin sheath (demyelination) renders axons vulnerable to a variety of insults. Axonal degeneration is well recognised in inflammatory demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis (MS) and also certain neurodegenerative diseases. Energy required for nerve impulse conduction and maintenance of structural integrity of axons is met by mitochondria. Based on the distribution of ion channels and the Na⁺/K⁺ ATPase, the energy requirements of demyelinated and dysmyelinated axons are likely to differ from myelinated axons. In this review we discuss the changes in mitochondrial presence within axons in relation to presence or absence of healthy myelin sheaths and propose the increase in mitochondrial presence following demyelination as an adaptive process. An energy deficit within demyelinated axons is likely to be more detrimental compared to myelinated axons, judging by the neuropathological findings in primary mitochondrial disorders due to mitochondrial and nuclear DNA mutations and the mitochondrial changes that follow demyelination. Agents that enhance and protect mitochondria, as potential therapy, need to be considered and investigated in earnest for demyelinating disorders of the CNS such as MS.