Identification of the abnormalities in astrocytic functions as potential drug targets for neurodegenerative disease

Expert Opin Drug Discov. 2024 May;19(5):603-616. doi: 10.1080/17460441.2024.2322988. Epub 2024 Feb 26.

Abstract

Introduction: Historically, astrocytes were seen primarily as a supportive cell population within the brain; with neurodegenerative disease research focusing exclusively on malfunctioning neurons. However, astrocytes perform numerous tasks that are essential for maintenance of the central nervous system`s complex processes. Disruption of these functions can have negative consequences; hence, it is unsurprising to observe a growing amount of evidence for the essential role of astrocytes in the development and progression of neurodegenerative diseases. Targeting astrocytic functions may serve as a potential disease-modifying drug therapy in the future.

Areas covered: The present review emphasizes the key astrocytic functions associated with neurodegenerative diseases and explores the possibility of pharmaceutical interventions to modify these processes. In addition, the authors provide an overview of current advancement in this field by including studies of possible drug candidates.

Expert opinion: Glial research has experienced a significant renaissance in the last quarter-century. Understanding how disease pathologies modify or are caused by astrocyte functions is crucial when developing treatments for brain diseases. Future research will focus on building advanced models that can more precisely correlate to the state in the human brain, with the goal of routinely testing therapies in these models.

Keywords: Astrocyte; BBB; glutamate uptake; neurodegeneration; neuroinflammation; oxidative stress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes* / drug effects
  • Astrocytes* / metabolism
  • Brain / physiopathology
  • Disease Progression
  • Drug Development* / methods
  • Humans
  • Molecular Targeted Therapy
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / physiopathology
  • Neurons / drug effects