title: Astroglia as a cellular target for neuroprotection and treatment of neuro-psychiatric disorders.
abstract: Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem-cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability. Support of neuroprotective functions of astrocytes is thus an important strategy for enhancing neuronal survival and improving outcomes in disease states. In this review, we first briefly examine how astrocytic dysfunction contributes to major neurological disorders, which are traditionally associated with malfunctioning of processes residing in neurons. Possible molecular entities within astrocytes that could underpin the cause, initiation and/or progression of various disorders are outlined. In the second section, we explore opportunities enhancing neuroprotective function of astroglia. We consider targeting astrocyte-specific molecular pathways which are involved in neuroprotection or could be expected to have a therapeutic value. Examples of those are oxidative stress defense mechanisms, glutamate uptake, purinergic signaling, water and ion homeostasis, connexin gap junctions, neurotrophic factors and the Nrf2-ARE pathway. We propose that enhancing the neuroprotective capacity of astrocytes is a viable strategy for improving brain resilience and developing new therapeutic approaches.
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, BS8 1TD, United Kingdom.
authors.forename: Beihui
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, BS8 1TD, United Kingdom.
authors.forename: Anja G
authors.initials: AG
authors.lastname: Teschemacher
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, BS8 1TD, United Kingdom.|Institute for Chemistry and Biology, Baltic Federal University, Kaliningrad, Russian Federation.
authors.forename: Sergey
authors.identifier: 0000-0002-1824-1764
authors.initials: S
authors.lastname: Kasparov
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents
keywords: astrocytes; astrocytic dysfunction; neurodegenerative disease; therapeutic targets