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Regulation of Intra...
Regulation of Intracellular Copper by Induction of Endogenous Metallothioneins Improves the Disease Course in a Mouse Model of Amyotrophic Lateral Sclerosis
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- Tokuda, Eiichi (författare)
- Umeå universitet,Klinisk kemi
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Watanabe, Shunsuke (författare)
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Okawa, Eriko (författare)
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Ono, Shin-ichi (författare)
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(creator_code:org_t)
- 2015-03-12
- 2015
- Engelska.
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Ingår i: Neurotherapeutics. - : Springer Science and Business Media LLC. - 1933-7213 .- 1878-7479. ; 12:2, s. 461-476
- Relaterad länk:
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease. The pathogenesis of the disease is poorly understood, but intracellular copper dyshomeostasis has been implicated as a key process in the disease. We recently observed that metallothioneins (MTs) are an excellent target for the modification of copper dyshomeostasis in a mouse model of ALS (SOD1(G93A)). Here, we offer a therapeutic strategy designed to increase the level of endogenous MTs. The upregulation of endogenous MTs by dexamethasone, a synthetic glucocorticoid, significantly improved the disease course and rescued motor neurons in SOD1(G93A) mice, even if the induction was initiated when peak body weight had decreased by 10 %. Neuroprotection was associated with the normalization of copper dyshomeostasis, as well as with decreased levels of SOD1(G93A) aggregates. Importantly, these benefits were clearly mediated in a MT-dependent manner, as dexamethasone did not provide any protection when endogenous MTs were abolished from SOD1(G93A) mice. In conclusion, the upregulation of endogenous MTs represents a promising strategy for the treatment of ALS linked to mutant SOD1.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Amyotrophic lateral sclerosis
- Copper dyshomeostasis
- Dexamethasone
- Metallothioneins
- Superoxide dismutase-1
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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