Genetic targeting of astrocytes to combat neurodegenerative disease

Abstract

Astrocytes, glial cells that interact extensively with neurons and other support cells throughout the central nervous system, have recently come under the spotlight for their potential contribution to, or potential regenerative role in a host of neurodegenerative disorders. It is becoming increasingly clear that astrocytes, in concert with microglial cells, activate intrinsic immunological pathways in the setting of neurodegenerative injury, although the direct and indirect consequences of such activation are still largely unknown. We review the current literature on the astrocyte's role in several neurodegenerative diseases, as well as highlighting recent advances in genetic manipulation of astrocytes that may prove critical to modulating their response to neurological injury, potentially combatting neurodegenerative damage.

Keywords: Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; glia; immune system; inflammation; reactive astrocyte; regeneration.

Figure 1

Bidirectional interaction between astrocytes and microglia in regulating neuroinflammation. Shown is a schematic of the coordinated astrocyte-microglia response to an inflammatory insult, as well as the coordinated de-escalation and return to non-reactive or resting state, respectively. IL: Interleukin; NO: nitrous oxide; NT: neurotransmitter; TNF: tumor necrosis factor.