The “molecular soldiers” of the CNS: Astrocytes, a comprehensive review on their roles and molecular signatures

Rupareliya, Vimal P.; Singh, Aditya A.; Butt, Ayub Mohammed; A, Hariharan; Kumar, Hemant

doi:10.1016/j.ejphar.2023.176048

Cited by 7 publications

(5 citation statements)

References 156 publications

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“…Indeed, C3, highly upregulated in A1-like and absent in A2-like astrocytes, was massively represented in post-mortem tissues from ALS, Alzheimer's disease, Huntington's disease, Parkinson's disease, and multiple sclerosis. This evidence demonstrates that A1-like astrocytes are present in most neurodegenerative diseases and probably retain a non-marginal role in neuronal death [64,74].…”

Section: Astrocytes and Neuroinflammation In Alsmentioning

confidence: 75%

The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity

Provenzano,

Torazza,

Bonifacino

et al. 2023

IJMS

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In the last two decades, there has been increasing evidence supporting non-neuronal cells as active contributors to neurodegenerative disorders. Among glial cells, astrocytes play a pivotal role in driving amyotrophic lateral sclerosis (ALS) progression, leading the scientific community to focus on the “astrocytic signature” in ALS. Here, we summarized the main pathological mechanisms characterizing astrocyte contribution to MN damage and ALS progression, such as neuroinflammation, mitochondrial dysfunction, oxidative stress, energy metabolism impairment, miRNAs and extracellular vesicles contribution, autophagy dysfunction, protein misfolding, and altered neurotrophic factor release. Since glutamate excitotoxicity is one of the most relevant ALS features, we focused on the specific contribution of ALS astrocytes in this aspect, highlighting the known or potential molecular mechanisms by which astrocytes participate in increasing the extracellular glutamate level in ALS and, conversely, undergo the toxic effect of the excessive glutamate. In this scenario, astrocytes can behave as “producers” and “targets” of the high extracellular glutamate levels, going through changes that can affect themselves and, in turn, the neuronal and non-neuronal surrounding cells, thus actively impacting the ALS course. Moreover, this review aims to point out knowledge gaps that deserve further investigation.

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Section: Astrocytes and Neuroinflammation In Alsmentioning

confidence: 75%

The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity

Provenzano,

Torazza,

Bonifacino

et al. 2023

IJMS

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“…In fact, they can be activated to the pro-inflammatory neurotoxic A1 phenotype through several mechanisms that are, in many cases, triggered and mediated by activated microglia, thus contributing to neurodegeneration, or to the A2 phenotype as a protective mechanism allowing recovery from damage [2]. Additionally, heterogeneous populations of astrocytes have been discovered depending on the brain area, thus adding further complexity to their physiological and pathological roles [3]. Astrocytes are also key components of the so-called "glymphatic" system which allows for the correct clearance of waste and toxic substances from the brain parenchyma and whose compromission is emerging as a key element contributing to several brain pathologies, as recently reviewed in [4].…”

Section: Heterogeneity and Roles Of Glial Cells In Neurodegenerative ...mentioning

confidence: 99%

Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies

Magni,

Riboldi,

Ceruti

2024

Cells

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In vitro and preclinical in vivo research in the last 35 years has clearly highlighted the crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes and satellite glial cells/Schwann cells in the central and peripheral nervous system, respectively. Several possible pharmacological targets to various neurodegenerative disorders and painful conditions have therefore been successfully identified, including receptors and enzymes, and mediators of neuroinflammation. However, the translation of these promising data to a clinical setting is often hampered by both technical and biological difficulties, making it necessary to perform experiments on human cells and models of the various diseases. In this review we will, therefore, summarize the most relevant data on the contribution of glial cells to human pathologies and on their possible pharmacological modulation based on data obtained in post-mortem tissues and in iPSC-derived human brain cells and organoids. The possibility of an in vivo visualization of glia reaction to neuroinflammation in patients will be also discussed.

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“…The A1 phenotype is involved in neuroinflammatory processes, and the A2 phenotype is considered neuroprotective. Classically, microglia can induce the A1 phenotype through IL-1β [ 19 ].…”

Section: Tlr Expression and Function In Glial Cells And Neuronsmentioning

confidence: 99%

From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System

Abarca-Merlin,

Martínez-Durán,

Medina-Pérez

et al. 2024

IJMS

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Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated with stress and cellular damage. TLRs are expressed in resident immune cells and both neurons and glial cells of the nervous system. Increasing evidence is emerging on the participation of TLRs not only in the immune response but also in processes of the nervous system, such as neurogenesis and cognition. Below, we present a review of the literature that evaluates the expression and role of TLRs in processes such as neurodevelopment, behavior, cognition, infection, neuroinflammation, and neurodegeneration.

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The “molecular soldiers” of the CNS: Astrocytes, a comprehensive review on their roles and molecular signatures

Cited by 7 publications

References 156 publications

The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity

The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity

Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies

From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System

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