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Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression.

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Acknowledgments

We thank Drs. Chunyan Li and Xiao-Yun Liu for helpful discussions of this article. This work was supported by grants from the Muscular Dystrophy Association (157511 and 254530 to X.W.), the ALS Therapy Alliance (to X.W.), and the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NS55072 to X.W.).

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Authors and Affiliations

  1. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Rachna S. Pandya, Wei Li & Xin Wang

  2. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA

    Haining Zhu

  3. Division of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA

    Robert Bowser

  4. Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Robert M. Friedlander

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  1. Rachna S. Pandya
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  2. Haining Zhu
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  3. Wei Li
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  5. Robert M. Friedlander
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  6. Xin Wang
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Correspondence to Xin Wang.

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Pandya, R.S., Zhu, H., Li, W. et al. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis. Cell. Mol. Life Sci. 70, 4729–4745 (2013). https://doi.org/10.1007/s00018-013-1415-0

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  • DOI: https://doi.org/10.1007/s00018-013-1415-0

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