Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

Abstract

Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer’s and Parkinson’s disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players.

A connexin43/YAP axis regulates astroglial-mesenchymal transition in hemoglobin induced astrocyte activation

“…Being the most dominant glial cells in the central nervous system (CNS), astrocytes provide neurotrophic and structural support to neurons and help maintain the extracellular milieu homeostasis [5][6][7][8]. Astrocyte activation is a common response to insults to the CNS including neurotrauma, infection, ischemia, hemorrhagic stroke, and neurodegeneration [9][10][11][12][13]. Reactive astrogliosis includes a series of continuous changes: alterations in gene and protein Edited by: N. Bazan.…”

Comparing the role of Ginkgolide B and Ginkgolide K on cultured astrocytes exposed to oxygen‑glucose deprivation

“…They are also a critical structural and functional part of synapses ( 3 , 4 ) and the neurovascular unit ( 5 , 6 ), and communicate with neurons and endothelial cells ( 7 , 8 ), contributing to angiogenesis, neurogenesis, and synaptic plasticity. Additionally, astrocytes are primary responders to CNS injury such as infection, trauma, ischemia and neurodegenerative disease, where they either exert critical beneficial neuroprotective and neurorestorative effects or play detrimental roles by triggering glutamate excitotoxicity, inflammatory molecule release and oxidative stress ( 9 – 11 ). Thus, to develop successful clinical neuroprotective and neurorestorative strategies, further investigation targeted on astrocytes is need for a promising therapeutic target of pharmacological and cell-based approaches.…”

Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats

“…These events may predispose to significant complications, non-resolved inflammation, and persistent cognitive impairments especially to frail and elderly subjects (Perry et al, 2007 ; Cunningham et al, 2009 ). Microglia activation is a known hallmark of neuroinflammation (Lucin and Wyss-Coray, 2009 ) but other cell types in the CNS like astrocytes have been also implicated in inflammatory signaling and brain plasticity (Dong and Benveniste, 2001 ; Capani et al, 2016 ). During ageing, astrocytes demonstrate phenotypical changes that have been associated with cells that express a senescence-associated secretory phenotype (SASP; Campisi, 2005 ).…”