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Important Genetic Factors in Multiple System Atrophy

Mutation in COQ2 gene discovered in both familial and sporadic MSA

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University Hospital
2013/07/03

Multiple system atrophy (MSA) is an intractable neurodegenerative disease that has long puzzled neurologists. MSA is characterized by the development of cytoplasmic aggregates of α-synuclein primarily in oligodendroglia, supporting cells that insulate the axons of neurons in the central nervous system. The pathogenic mechanisms underlying MSA, however, remain unknown, making it difficult to develop efficacious therapies. An international collaborative team led by Professor Shoji Tsuji at the University of Tokyo, including other institutions across Japan, Europe and the United States have come together to dissect the molecular mechanisms of MSA.

© Shoji Tsuji. Functionally impaired variants of COQ2 were associated with an increased risk of multiple system atrophy in both familial and sporadic patients.

Although MSA has been defined as a nongenetic disorder until recently, several multiplex MSA families (where more than one family member develops the disease) have recently been discovered, indicating that strong genetic factors confer susceptibility to the disease in families. Focusing on rare multiplex families with MSA and applying massively parallel sequencing technologies, the team has revealed novel genetic changes (mutations in the COQ2 gene) underlying the pathogenesis of both familial and sporadic (non-familial) MSA. The COQ2 gene encodes an enzyme, COQ2, essential for biosynthesis of coenzyme Q10. Their findings suggest that impaired COQ2 activity, which would be predicted to impair the mitochondrial respiratory chain and increase vulnerability to oxidative stress, leads to susceptibility to MSA.

This discovery is a promising starting point for the development of therapies for this intractable neurodegenerative disease.

Press release (Japanese)

Paper

Mitsui J, Matsukawa T, Ishiura, H, et al.,
“Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy”,
The New England Journal of Medicine Online Edition: 2013/6/12, doi: 10.1056/NEJMoa1212115.
Article link

Links

Graduate School of Medicine

Neuroscience, Graduate School of Medicine

Department of Neurology, Neuroscience, Graduate School of Medicine

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