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Exp Neurobiol 2014; 23(4): 337-344
Published online December 31, 2014
https://doi.org/10.5607/en.2014.23.4.337
© The Korean Society for Brain and Neural Sciences
Joanna H. Wong1,2, Glenda M. Halliday1,2 and Woojin Scott Kim1,2*
1Neuroscience Research Australia, Sydney, NSW 2031,
2School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Correspondence to: *To whom correspondence should be addressed.
TEL: 61 2 9399 1000, FAX: 61 2 9399 1005
e-mail: w.kim@unsw.edu.au
Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of α-synuclein aggregates in the brain and therefore MSA is classified as an α-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of α-synuclein partly overlap with other α-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for α-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein.
Keywords: Multiple system atrophy, oligodendrocyte, α-synuclein, myelin, lipid dyshomeostasis