Contribution of astrocytes to neuropathology of neurodegenerative diseases

Acıoğlu, Çiğdem; Li, Lun; Elkabes, Stella

doi:10.1016/j.brainres.2021.147291

Cited by 76 publications

(57 citation statements)

References 298 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Astrocytes respond to CNS injury and disease by producing many different cytokines and inflammatory mediators [ 20 , 21 ]. In this study, we investigated the effects of CBD on the responses of primary mouse astrocytes to LPS, a ligand that binds TLR4, one of the most common receptors recognizing PAMPs/DAMPs [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Astrocytes are the most abundant and one of the most important glial cell populations in the CNS. They regulate the blood-brain barrier (BBB), neuronal metabolism, electrical transmission, CNS development and repair [ 20 , 21 ]. It is also known that astrocytes are involved in neuroinflammation [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…They regulate the blood-brain barrier (BBB), neuronal metabolism, electrical transmission, CNS development and repair [ 20 , 21 ]. It is also known that astrocytes are involved in neuroinflammation [ 20 , 21 ]. Previously, CBD was found to inhibit β–amyloid (Aβ)-induced inflammatory mediators (TNF-α, S100B, and IL-1) from rat primary astrocytes [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia

Chen

Liu

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Cannabidiol (CBD) exhibits anti-inflammatory and neuroprotective properties and is suggested to be effective in the pre-clinical and clinical treatment of illnesses of the central nervous system (CNS). Two major types of CNS glial cells, astrocytes and microglia, play critical roles in the development and pathogenesis of CNS diseases. However, the mechanisms by which CBD plays an anti-inflammatory and neuroprotective role for these glial cells have not been fully elucidated. In this study, we examined the effects of CBD on the inflammatory response of mouse primary astrocytes and microglia. We also investigated whether the effect of CBD on cytokine release is mediated by the G protein coupled receptor 3 (GPR3), which was recently identified as a novel receptor for CBD. Our results showed that CBD inhibited inflammatory responses of astrocytes and microglia stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand in vitro and in vivo. In addition, CBD reduced the phosphorylation of STAT3 and NF-κB signaling pathways in LPS-stimulated astrocytes. However, the inhibitory effect of CBD on pro-inflammatory cytokine production was independent of GPR3 expression in both types of glial cells. Thus, although CBD is effective in ameliorating the activation of astrocytes and microglia, its mechanism of action still requires further study. Our data support the concept that CBD may have therapeutic potential for neurological disorders that involve neuroinflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia

Chen

Liu

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The role of reactive astrocytes in neurodegenerative diseases in not well understood. The questions whether reactive astrocytes are neurotoxic or neuroprotective, and whether their normal physiological functions are undermined remain unsettled [ 3 – 5 ]. Another important question is whether animal models faithfully reproduce glial phenotypes associated with neurodegenerative diseases in humans [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

The degree of astrocyte activation is predictive of the incubation time to prion disease

Makarava

Mychko

Chang

et al. 2021

acta neuropathol commun

View full text Add to dashboard Cite

In neurodegenerative diseases including Alzheimer’s, Parkinson’s and prion diseases, astrocytes acquire disease-associated reactive phenotypes. With growing appreciation of their role in chronic neurodegeneration, the questions whether astrocytes lose their ability to perform homeostatic functions in the reactive states and whether the reactive phenotypes are neurotoxic or neuroprotective remain unsettled. The current work examined region-specific changes in expression of genes, which report on astrocyte physiological functions and their reactive states, in C57Black/6J mice challenged with four prion strains via two inoculation routes. Unexpectedly, strong reverse correlation between the incubation time to the diseases and the degree of astrocyte activation along with disturbance in functional pathways was observed. The animal groups with the most severe astrocyte response and degree of activation showed the most rapid disease progression. The degree of activation tightly intertwined with the global transformation of the homeostatic state, characterized by disturbances in multiple gene sets responsible for normal physiological functions producing a neurotoxic, reactive phenotype as a net result. The neurotoxic reactive phenotype exhibited a universal gene signature regardless of the prion strain. The current work suggests that the degree of astrocyte activation along with the disturbance in their physiological pathways contribute to the faster progression of disease and perhaps even drive prion pathogenesis.

show abstract

“…The emerging view is that astrocytes are potential new targets for therapeutic interventions. A comprehensive understanding of astrocyte heterogeneity and disease-specific phenotypic complexity could facilitate the design of novel strategies to treat neurodegenerative disorders [9].…”

Section: Introductionmentioning

confidence: 99%

Astrocytes and their Phenomenal Possibilities in the Treatment of Various Neurodegenerative Disorders: An Overview

Maslova

Bazaeva

Abdullaeva

et al. 2021

JPRI

View full text Add to dashboard Cite

At present, research in the field of the brain does not cease to surprise us with new facts and discoveries that no one could have suspected about 30 years ago. But it was at the time when it became clear that the cerebral neurons are not the only cells that can respond to changes in the external environment. A real scientific boom began to study a heterogeneous group called glia. And scientists are paying close attention to the largest of them – astrocytes. Understanding the importance of astrocytes in the mechanisms of repair and damage to brain cells in various forms of CNS pathology determines the possibility of targeted search for drugs that affect the rate of development of reactive astrogliosis in response to various brain injuries. At the same time, pharmacological modulation of activated astrocytes and other components of glia can be an integral part of the therapy of neurological diseases.

show abstract

Contribution of astrocytes to neuropathology of neurodegenerative diseases

Cited by 76 publications

References 298 publications

Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia

Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia

The degree of astrocyte activation is predictive of the incubation time to prion disease

Astrocytes and their Phenomenal Possibilities in the Treatment of Various Neurodegenerative Disorders: An Overview

Contact Info

Product

Resources

About