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Redox Regulation and Misfolding of SOD1: Therapeutic Strategies for Amyotrophic Lateral Sclerosis

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Redox-Active Therapeutics

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Abstract

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease that affects upper and lower motor neurons leading to paralysis and death within 2–5 years after disease onset. The only FDA-approved drug currently used for ALS treatment is Riluzole, which improves survival by 2–3 months. The need for understanding the pathology of ALS and development of therapeutics is therefore still strong. A subset of familial ALS patients has mutations in Cu, Zn-superoxide dismutase (SOD1) that results in a toxic gain-of-function. In this review, the main hypotheses of SOD1 toxic gain-of-function properties are explained and evidence for the role of SOD1 in sporadic ALS is discussed. Of the wide variety of therapeutic strategies currently being developed, we have reviewed therapeutic strategies that focus on the role of SOD1 in the pathology of ALS. These include modification of cysteine 111, restoring SOD1 metal content and decreasing oxidative stress and immunization.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

CSF:

Cerebrospinal fluid

FALS:

Familial ALS

HD:

Huntington’s disease

SALS:

Sporadic ALS

SOD1:

Cu, Zn-superoxide dismutase

TG2:

Transglutaminase 2

WT:

Wild type

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  1. Department of Biology, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan

    Wouter Hubens & Ayako Okado-Matsumoto

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  1. Duke University School of Medicine, Durham, North Carolina, USA

    Ines Batinić-Haberle

  2. Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil

    Júlio S. Rebouças

  3. Duke University School of Medicine, Durham, North Carolina, USA

    Ivan Spasojević

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Hubens, W., Okado-Matsumoto, A. (2016). Redox Regulation and Misfolding of SOD1: Therapeutic Strategies for Amyotrophic Lateral Sclerosis. In: Batinić-Haberle, I., Rebouças, J., Spasojević, I. (eds) Redox-Active Therapeutics. Oxidative Stress in Applied Basic Research and Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-30705-3_27

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