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Melatonin and Other Neuroprotective Agents Target Molecular Mechanisms of Disease in Amyotrophic Lateral Sclerosis

  • Anastasios Fotinos
  • Yongjin Zhu
  • Lilly L. J. Mao
  • Nazem Atassi
  • Edward W. Zhou
  • Sarfraz Ahmad
  • Yingjun Guan
  • James D. Berry
  • Merit E. Cudkowicz
  • Xin Wang
Chapter

Abstract

Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weakness, weight loss, and respiratory failure. Evidence suggests that various molecular mechanisms including oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity, proteasomal dysfunction, and inflammation are responsible for ALS pathogenesis. In this chapter we summarize the various therapies tested on animal models targeting the above molecular mechanisms and compare their effects on body weight loss, muscle damage, disease onset, duration, and survival. We also review drugs that prevent body weight loss in animal models of ALS and analyze their structure-activity relationship.

Keywords

Amyotrophic Lateral Sclerosis Motor Neuron Amyotrophic Lateral Sclerosis Patient G93A Mouse Body Weight Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Authors thank Drs. Rachna S. Pandya and Wei (David) Li for review discussion. This work is supported by grants from the MDA (to X. W.), the ALS Therapy Alliance (to X. W.), the Brigham and Women’s Hospital Biomedical Research Institute Fund to Sustain Research Excellence (to X. W.), the Bill & Melinda Gates Foundation (to X. W.), and the National Natural Science Foundation of China (81271413 to Y. G.).

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Copyright information

© Springer India 2016

Authors and Affiliations

  • Anastasios Fotinos
    • 1
  • Yongjin Zhu
    • 1
  • Lilly L. J. Mao
    • 2
  • Nazem Atassi
    • 3
  • Edward W. Zhou
    • 1
  • Sarfraz Ahmad
    • 2
  • Yingjun Guan
    • 4
  • James D. Berry
    • 3
  • Merit E. Cudkowicz
    • 3
  • Xin Wang
    • 1
  1. 1.Department of NeurosurgeryBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Aimcan Pharma Research and Technologies Inc.GuelphCanada
  3. 3.Neurological Clinical Research InstituteMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Department of Histology and EmbryologyWeifang Medical UniversityWeifang, ShandongChina

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