Astrogliosis as a therapeutic target for neurodegenerative diseases

• Published in: Neuroscience letters Vol. 565; pp. 59 - 64
• Main Authors: Colangelo, Anna Maria, Alberghina, Lilia, Papa, Michele
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 17.04.2014
• Subjects: Animals; Astrocytes - pathology; Astrocytes - transplantation; Brain - drug effects; Brain - pathology; Brain homeostasis; Drug Discovery; Gliosis - pathology; Gliosis - therapy; Glutamic Acid - metabolism; Humans; Inflammation - drug therapy; Inflammation - pathology; Nerve Growth Factors - metabolism; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - therapy; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurotrophins; Reactive astrogliosis; Signal Transduction; Synapses - physiology; Systems Biology; Reactive astrogliosis; NO; Neuroprotection; TNFα; JNK; ALS; CNS; Iba1; COX-1/2; LPS; GLAST; PI3K; EAAT1/2; NMDA; EAAC1; Brain homeostasis; Neurotrophins; GSH; vGLUT1; AD; BDNF; MS; MMPs; STAT3; EAE; PLCγ; MAPK; NGF; IP3; i.t; GFAP; vGAT; PD; Ca2; Systems biology; GlyT-1; GABA; SCI; HD; ATP; BB14; GLT-1
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.01.014

•We briefly review the role of astrocytes in brain function.•We review the main pathways in astrocytic dysfunction.•We focus on astroglial-specific targets for clinical management of neurodegenerative disorders.•We describe the usefulness of a systems biology approach in drug discovery for neurodegenerative disorders. Chronic neurodegenerative diseases represent major unmet needs for therapeutic interventions. Recently, the neurocentric view of brain function and disease has been challenged by a great number of evidence supporting the physiopathological potential of neuroglia. Astrocytes, in particular, play a pivotal role in brain homeostasis as they actively participate in neuronal metabolism, synaptic plasticity and neuroprotection. Furthermore, they are intrinsic components of brain responses to toxic and traumatic insults through complex processes involving several molecular and functional alterations that may lead to disruption of brain homeostasis and connectivity. This review provides a brief overview of current knowledge of astrocyte functions in the brain, and focuses on some glial-specific pathways involved in astrocytic dysfunction that might be effective therapeutic targets for clinical management of neurodegenerative disorders.