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

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
• neurodegeneration
• glutamate uptake
• neuroinflammation
• oxidative stress
• BBB

Article highlights

• The view of astrocytes has evolved from static supporting cells to complex, multifunctional players in CNS function having an active role in processes such as neurotransmitter uptake, calcium signaling, metabolic support and inflammatory response

• Astrocytes become dysfunctional in several neurodegenerative diseases, including AD, PD, and ALS

• Several molecules mediating distinct astrocytic functions have been recognized to have therapeutic potential

• Promising preliminary data have been obtained from studies of astrocyte-modulating drugs

• Drug development targeting astrocytes is an active area of research. Further understanding of astrocytic biology and their involvement in neurodegenerative disease may lead to more precise therapeutic interventions in the future

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are funded by the Research Council of Finland via grant no. 334525 and by Sigrid Juselius Foundation [via award nos. 0055 and 0056].