Therapeutic Strategies Under Development Targeting Inflammatory Mechanisms in Amyotrophic Lateral Sclerosis

Sebastiano Giuseppe Crisafulli, Simona Brajkovic, Maria Sara Cipolat Mis, Valeria Parente, Stefania Corti

Research output: Contribution to journalArticlepeer-review

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of cortical, bulbar, and spinal motor neurons (MNs). The cardinal manifestation of ALS is a progressive paralysis which leads to death within a time span of 3 to 5 years after disease onset. Despite similar final output of neuronal death, the underlying pathogenic causes are various and no common cause of neuronal damage has been identified to date. Inflammation-mediated neuronal injury is increasingly recognized as a major factor that promotes disease progression and amplifies the MN death-inducing processes. The neuroimmune activation is not only a physiological reaction to cell-autonomous death but is an active component of nonautonomous cell death. Such injury-perpetuating phenomenon is now proved to be a common mechanism in many human disorders characterized by progressive neurodegeneration. Therefore, it represents an interesting therapeutic target. To date, no single cell population has been proved to play a major role. The existing evidence points to a complex cross talk between resident immune cells and nonresident cells, like monocytes and T lymphocytes, and to a dysregulation in cytokine profile and in phenotype commitment. After a summary of the most important mechanisms involved in the inflammatory reaction in ALS, this review will focus on novel therapeutic tools that rely on tackling inflammation to improve motor function and survival. Herein, completed, ongoing, or planned clinical trials, which aim to modify the rapidly fatal course of this disease, are discussed. Anti-inflammatory compounds that are currently undergoing preclinical study and novel suitable molecular targets are also mentioned.

Original languageEnglish
Pages (from-to)2789-2813
Number of pages25
JournalMolecular Neurobiology
Volume55
Issue number4
DOIs
Publication statusPublished - 2018

Keywords

  • ALS
  • ALS progression
  • Anti-inflammatory drugs
  • Astrocytes
  • Inflammation
  • Microglia
  • Motor neurons
  • Neurodegeneration

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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