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ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
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Motor Neuron Susceptibility in ALS/FTD.

Audrey M G Ragagnin1, Sina Shadfar1, Marta Vidal1

  • 1Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

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|July 19, 2019
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Summary

Amyotrophic lateral sclerosis (ALS) selectively targets motor neurons (MNs). This review explores intrinsic MN factors and network properties contributing to specific MN subtype vulnerability in ALS.

Keywords:
amyotrophic lateral sclerosisfast and slow motor unitsfrontotemporal dementianeurodegenerationselective vulnerability

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Area of Science:

  • Neuroscience
  • Neurology
  • Cell Biology

Background:

  • Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder.
  • It is characterized by the selective loss of upper and lower motor neurons (MNs).
  • The precise mechanisms driving MN degeneration and selective vulnerability remain largely unknown.

Purpose of the Study:

  • To review intrinsic factors within MNs that confer susceptibility to neurodegeneration in ALS.
  • To investigate reasons for differential vulnerability among MN subpopulations.
  • To examine the role of anatomical networks and the microenvironment in MN degeneration.

Main Methods:

  • This is a review article, synthesizing existing research.
  • It focuses on molecular and physiological properties of MNs.
  • It analyzes anatomical and microenvironmental factors impacting MNs.

Main Results:

  • Specific MN subpopulations exhibit differential vulnerability in ALS.
  • Intrinsic MN properties and extrinsic factors contribute to this selective targeting.
  • Corticospinal and lower somatic MNs are more susceptible than resistant MN subgroups.

Conclusions:

  • Understanding MN-intrinsic factors is crucial for elucidating ALS pathogenesis.
  • MN subtype vulnerability is determined by a combination of molecular, physiological, and network properties.
  • Further research into these factors may reveal therapeutic targets for ALS.