著者

徳田 栄一 Stefan L. Marklund 古川 良明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.7, pp.1015-1019, 2019-07-01 (Released:2019-07-01)

参考文献数

16

被引用文献数

2 2

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Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that is characterized by the loss of motor neurons, which results in progressive muscle atrophy. The pathology spreads from the initial site of onset to contiguous anatomic regions. Mutations in the gene encoding Cu/Zn-superoxide dismutase (SOD1) have been identified in a dominantly inherited form of ALS (ALS-SOD1). A major hallmark of ALS-SOD1 is the abnormal accumulation of conformationally aberrant SOD1 protein (i.e., misfolded SOD1) within motor neurons. Emerging experimental evidence has suggested that misfolded proteins associated with neurodegenerative diseases exhibit prion-like properties, i.e., misfolded proteins act as conformational templates that convert normal proteins into a pathogenic form. Possibly as a result of this prion-like self-propagation property, misfolded forms of pathological proteins are considered to accumulate in the central nervous system and cause neurodegeneration. In this article, we review recent evidence for the role of prion-like mechanisms in ALS-SOD1. In particular, we discuss the propensity of misfolded SOD1 to act as a pathological seed, spread between cells, and propagate neuroanatomically.

著者

古川 良明

出版者

一般社団法人 日本生物物理学会

雑誌

生物物理 (ISSN:05824052)

巻号頁・発行日

vol.60, no.6, pp.338-341, 2020 (Released:2020-11-28)

参考文献数

20

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Mutations in the gene coding Cu/Zn-superoxide dismutase (SOD1) are known to cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease with no cures. SOD1 is a highly stable enzyme where copper and zinc ions bind and a disulfide bond forms, but is also known to accumulate as misfolded forms in spinal motoneurons of ALS. A key to understand such pathological changes in SOD1 is the contribution of metal binding as well as disulfide formation to the conformational stability of SOD1. In this review, I will summarize mechanisms of SOD1 misfolding in ALS where the metal binding and/or disulfide formation go awry.