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

Astroglia, an extended class of homeostatic and defensive cells of the central nervous system, contribute to the pathogenesis of all known neurological and neuropsychiatric disorders. 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 remodelling 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 non-proliferative 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 co-exist 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.