Old versus new mechanisms in the pathogenesis of ALS

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Amyotrophic Lateral Sclerosis (ALS) is recognized as a very complex disease. As we have learned in the past 20 years from studies in patients and in models based on the expression of mutant SOD1, ALS is not a purely motor neuron disease as previously thought. While undoubtedly motor neurons are lost in patients, a number of alterations in those cell-types that interact functionally with motor neurons (astrocytes, microglia, muscle fibers, oligodendrocytes) take place even long before onset of symptoms. At the same time, disturbance of several, only partly inter-related physiological functions play some role in the onset and progression of the disease. Traditionally, mitochondrial damage and oxidative stress, excitotoxicity, neuroinflammation, altered axonal transport, ER stress, protein aggregation and defective removal of toxic proteins have been considered as key factors in the pathogenesis of ALS, with the relatively recent addition of disturbances in RNA metabolism. This complexity makes the search for an effective treatment extremely difficult and prompts further studies to reveal other possible, previously unappreciated aspects of the pathogenesis of ALS. In this review, we focus on previous knowledge on ALS mechanisms as well as new facets emerging from studies on genetic ALS patients and models that may both provide precious information for a novel therapeutic approach.

Original languageEnglish
Pages (from-to)276-286
Number of pages11
JournalBrain Pathology
Volume26
Issue number2
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Neurons
Motor Neuron Disease
Axonal Transport
Poisons
Oligodendroglia
Microglia
Heat-Shock Proteins
Astrocytes
Disease Progression
Oxidative Stress
RNA
Muscles
Therapeutics
Proteins

Keywords

  • ALS
  • amyotrophic lateral sclerosis
  • motor neuron
  • protein aggregation
  • RNA metabolism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Old versus new mechanisms in the pathogenesis of ALS. / Rossi, Simona; Cozzolino, Mauro; Carrì, Maria Teresa.

In: Brain Pathology, Vol. 26, No. 2, 01.03.2016, p. 276-286.

Research output: Contribution to journalArticle

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