Curing the brain: in search for new astrocyte-specific therapies

Abstract

Astroglia, an extended class of homeostatic and defensive cells of the central nervous system (CNS), contribute to the pathogenesis of all known neurological and neuropsychiatric disorders. The pathophysiology of astrocytes is complex, mutable, disease and disease-stage specific. In neuroinflammatory lesions and in various chronic conditions, astrocytes undergo an evolutionary conserved defensive remodeling known as reactive astrogliosis, which produces highly heterogeneous reactive astrocytic phenotypes. Broadly, reactive astrogliosis can be classified into proliferative anysomorphic barrier-forming astrogliosis characteristic of traumatic CNS lesions and nonproliferative isomorphic gliosis widely manifested in chronic neuropathologies. In addition, in many pathologies, astrocytes undergo atrophy and asthenia with resulting loss of homeostatic support and neuroprotection precipitating neuronal damage. Reactive and atrophic astrocytes may coexist or emerge in sequence in a disease-stage-dependent manner. Several classes of astrocyte-specific molecules and processes implicated in various diseases of the CNS represent therapeutic targets. Astrocyte-specific therapeutic strategies may improve both disease-preventing and disease-modifying therapeutic outcomes.