Dopaminergic Signaling as a Plausible Modulator of Astrocytic Toll-Like Receptor 4: A Crosstalk between Neuroinflammation and Cognition.

Abstract

Neuroinflammation is one of the major pathological factors leading to Alzheimer's disease (AD). The role of microglial cells in neuroinflammation associated with AD has been known for a long time. Recently, astrocytic inflammatory responses have been linked to the neuronal degeneration and pathological development of AD. Lipopolysaccharide (LPS) and Amyloid Beta (Aβ) activate astrocytes and microglial cells via toll-like 4 (TLR4) receptors leading to neuroinflammation. Reactive (activated) astrocytes mainly comprising of A1 astrocytes (A1s) are involved in neuroinflammation, while A2 astrocytes (A2s) possess neuroprotective activity. Studies link low dopamine (DA) levels during the early stages of neurodegenerative disorders with its anti-inflammatory and immuoregulatory properties. DA mediates neuroprotection via inhibition of the A1 astrocytic pathway through blockade of NF-kB and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3); and promotion of A2 astrocytic pathways leading to the formation of neurotrophic factors like BDNF and GDNF. In this current review, we have discussed the crosstalk between the dopaminergic system in astrocytic TLR4 and NF-kB in addition to NLRP3 inflammasome in the modulation of neuroinflammatory pathologies in cognitive deficits.

• Authors: Prasada Chowdari Gurram, Suman Manandhar, Sairaj Satarker, Jayesh Mudgal, Devinder Arora, Madhavan Nampoothiri
• Journal: CNS & neurological disorders drug targets (CNS Neurol Disord Drug Targets) Vol. 22 Issue 4 Pg. 539-557 ( 2023) ISSN: 1996-3181 [Electronic] United Arab Emirates
• PMID: 35422229 (Publication Type: Review, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• NLR Family, Pyrin Domain-Containing 3 Protein
• Amyloid beta-Peptides
• Toll-Like Receptor 4
• NF-kappa B
• Dopamine
• Inflammasomes

Topics

• Humans
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Amyloid beta-Peptides (metabolism)
• Toll-Like Receptor 4 (metabolism)
• NF-kappa B (metabolism)
• Neuroinflammatory Diseases
• Dopamine (metabolism)
• Astrocytes (metabolism)
• Inflammasomes (metabolism)
• Alzheimer Disease (metabolism)
• Cognition
• Microglia (metabolism)