Reactive Astrocytes as Therapeutic Targets for Brain Degenerative Diseases: Roles Played by Metabotropic Glutamate Receptors

Abstract

Astrocytes are well known to play critical roles in the development and maintenance of the central nervous system (CNS). Moreover, recent reports indicate that these cells are heterogeneous with respect to the molecules they express and the functions they exhibit in the quiescent or activated state. Because astrocytes also contribute to pathology, promising new results raise the possibility of manipulating specific astroglial populations for therapeutic roles. In this mini-review, we highlight the function of metabotropic glutamate receptors (mGluRs), in particular mGluR3 and mGluR5, in reactive astrocytes and relate these to three degenerative CNS diseases: multiple sclerosis, Alzheimer's disease and Amyotrophic Lateral Sclerosis. Previous studies demonstrate that effects of these receptors may be beneficial, but this varies depending on the subtype of receptor, the state of the astrocytes, and the specific disease to which they are exposed. Elucidating the role of mGluRs on astrocytes at specific times during development and disease will provide novel insights in understanding how to best use these to serve as therapeutic targets.

Keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Astrocyte heterogeneity; Group I/II metabotropic glutamate receptors; Multiple sclerosis.

Fig. 1

Response of astrocytes to disease can be manipulated by mGluRs in a positive or negative direction depending on the state of astrocyte activation, the local astrocyte environment and the disease that is responsible for reactivity. Created with BioRender