Dopamine, Immunity, and Disease

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 75(1), P. 62 - 158

Published: Dec. 8, 2022

The neurotransmitter dopamine is a key factor in central nervous system (CNS) function, regulating many processes including reward, movement, and cognition. Dopamine also regulates critical functions peripheral organs, such as blood pressure, renal activity, intestinal motility. Beyond these functions, growing body of evidence indicates that an important immunoregulatory factor. Most types immune cells express receptors other dopaminergic proteins, take up, produce, store, and/or release dopamine, suggesting immunomodulation for function. Targeting pathways could be promising avenue the treatment inflammation disease, but despite increasing research this area, data on specific effects disease remain inconsistent poorly understood. Therefore, review integrates current knowledge role cell function inflammatory signaling across systems. We discuss understanding regulation CNS tissues, highlighting diseases Parkinson’s several neuropsychiatric conditions, neurologic human immunodeficiency virus, bowel rheumatoid arthritis, others. Careful consideration given to influence experimental design results, we note number areas need further research. Overall, our immunology at cellular, tissue, level prompts development therapeutics strategies targeted toward ameliorating through immunity.

Significance Statement

Canonically, recognized involved cognition, reward. However, acts modulator periphery. This comprehensively assesses pathogenesis cellular tissue level. will provide broad access information fields, identify investigation, drive therapeutic strategies.

Language: Английский

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Cognitive impairment in people living with HIV: consensus recommendations for a new approach

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(7), P. 424 - 433

Published: June 13, 2023

Language: Английский

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The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(8), P. 630 - 639

Published: July 12, 2022

Despite potent suppression of HIV-1 viral replication in the central nervous system (CNS) by antiretroviral therapy (ART), between 15% and 60% HIV-1-infected patients receiving ART exhibit neuroinflammation symptoms HIV-1-associated neurocognitive disorder (HAND) - a significant unmet challenge. We propose that emergence from latency microglia underlies both CNS progression HAND. Recent molecular studies cellular silencing mechanisms show can be reversed proinflammatory cytokines signals damaged neurons, potentially creating intermittent cycles reactivation brain. posit anti-inflammatory agents also block reactivation, such as nuclear receptor agonists, might provide new putative therapeutic avenues for treatment

Language: Английский

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The Impact of Neurotransmitters on the Neurobiology of Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15340 - 15340

Published: Oct. 19, 2023

Neurodegenerative diseases affect millions of people worldwide. result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction these functions is associated with Alzheimer's disease, Parkinson's Huntington's Amyotrophic lateral sclerosis, motor neuron disease. In addition these, 50% living HIV develop a spectrum cognitive, motor, and/or mood problems collectively referred as HIV-Associated Neurocognitive Disorders (HAND) despite widespread use combination antiretroviral therapies. Neuroinflammation neurotransmitter systems have pathological correlation play critical role developing neurodegenerative diseases. Each has unique pattern dysregulation system, which been attributed different forms cell-specific neuronal loss. this review, we will focus on discussion regulation dopaminergic cholinergic systems, more commonly disturbed disorders. Additionally, provide evidence hypothesis disturbances neurotransmission contribute loss observed Further, highlight dopamine mediator injury context NeuroHIV. This review need further investigate their etiology

Language: Английский

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α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 13, 2024

Abstract Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic is linked cognitive deficits LBD. Here, we investigated pathological impact αSyn on hippocampal neurons. We report that either overexpression or pre-formed fibrils (PFFs) treatment triggers formation cofilin-actin rods, synapse disruptors, cultured neurons synucleinopathy mouse models LBD patients. In vivo, cofilin pathology present concomitantly with impairment dysfunction. Rods generation prompted by involves co-action cellular prion protein (PrP C ) chemokine receptor 5 (CCR5). Importantly, show CCR5 inhibition, a clinically relevant peptide antagonist, reverts dendritic spine promoted αSyn. Collectively, detail molecular mechanism through which disrupts structure identify as novel therapeutic target prevent

Language: Английский

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Co-receptor signaling in the pathogenesis of neuroHIV

Retrovirology, Journal Year: 2021, Volume and Issue: 18(1)

Published: Aug. 24, 2021

Abstract The HIV co-receptors, CCR5 and CXCR4, are necessary for entry into target cells, interacting with the envelope protein, gp120, to initiate several signaling cascades thought be important process. Co-receptor may also promote development of neuroHIV by contributing both persistent neuroinflammation indirect neurotoxicity. But despite critical importance CXCR4 pathogenesis, there is only one therapeutic (the inhibitor Maraviroc) that targets these receptors. Moreover, our understanding co-receptor in specific context relatively poor. Research has largely stalled past decade, possibly owing complexity functions mediated Examining many pathways triggered activation been challenging due lack molecular tools targeting proteins involved wide array model systems used across experiments. Studies examining impact on neuropathogenesis often show multiple overlapping similar stimuli, leading contradictory data effects activation. To address this, we will broadly review infection neuropathogenesis, examine different functions, then discuss differences between induced cognate ligands. We assess focusing neuroinflammation. explore how use substances abuse, which highly prevalent people living HIV, can exacerbate neuropathogenic signaling. Finally, current state therapeutics highlighting challenges field faced areas research would yield most benefit infection. This discussion provide a comprehensive overview what known remains explored regard infection, emphasize potential value co-receptors as future development.

Language: Английский

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Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 643 - 643

Published: Jan. 7, 2022

HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% this population. Nowadays, HAND neuropathogenesis considered to be caused by infected cells that cross brain–blood barrier and produce viral proteins can secreted internalized into neurons leading disruption cellular processes. The evidence points such as Tat causal agent for neuronal alteration thus HAND. hallmarks Tat-induced neurodegeneration are endoplasmic reticulum stress mitochondrial dysfunction. Sirtuins (SIRTs) NAD+-dependent deacetylases involved mitochondria biogenesis, unfolded protein response, intrinsic apoptosis pathway. interaction with these causes inhibition SIRT1 SIRT3. Studies revealed SIRTs activation promotes neuroprotection neurodegenerative diseases Alzheimer’s Parkinson’s disease. Therefore, review focuses on neurotoxicity mechanisms involve key regulators their modulation a therapeutic strategy tackling thereby improving quality life people living HIV.

Language: Английский

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1H-NMR metabolomics investigation of CSF from children with HIV reveals altered neuroenergetics due to persistent immune activation

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: April 30, 2024

Background HIV can invade the central nervous system (CNS) early during infection, invading perivascular macrophages and microglia, which, in turn, release viral particles immune mediators that dysregulate all brain cell types. Consequently, children living with often present neurodevelopmental delays. Methods In this study, we used proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy to analyze neurometabolic profile of infection using cerebrospinal fluid samples obtained from 17 HIV+ 50 HIV− South African children. Results Nine metabolites, including glucose, lactate, glutamine, 1,2-propanediol, acetone, 3-hydroxybutyrate, acetoacetate, 2-hydroxybutyrate, myo-inositol, showed significant differences when comparing infected those uninfected. These metabolites may be associated activation innate response disruption neuroenergetics pathways. Conclusion results elucidate state HIV, upregulation glycolysis, dysregulation ketone body metabolism, elevated reactive oxygen species production. Furthermore, hypothesize neuroinflammation alters astrocyte–neuron communication, lowering neuronal activity which contribute delay observed population.

Language: Английский

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Mechanism of Gastrodin against neurotoxicity based on network pharmacology, molecular docking and experimental verification

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117611 - 117611

Published: Oct. 25, 2024

Language: Английский

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Graph theory analysis reveals functional brain network alterations in HIV-associated asymptomatic neurocognitive impairment in virally suppressed homosexual males

BMC Infectious Diseases, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 25, 2025

This study aimed to investigate the global and nodal functional network alterations, abnormal connections of brain regions, potential imaging biomarkers in virally suppressed people living with HIV (PLH) asymptomatic neurocognitive impairment (ANI) using graph theory analysis. The included 64 men ANI (mean age 32.45 years) healthy controls (HC) 31.31 years). was established through method Automated Anatomic Labeling (AAL) 90 atlas, which provides a cerebrum parcellation framework. Moreover, hub regions were identified based on betweenness centrality (Bc). Functional connectivity (FC) differences investigated between two groups, these located resting-state (RSN). Neuropsychological (NP) tests performed, relationships measures, clinical data, NP analyzed. Multiple comparisons used correct for false-positive findings. On level, small-worldness, efficiency (Eg), local (Eloc) significantly decreased subjects. frontal subcortical showed while parietal, temporal, occipital lobes increased measures. Increased FCs found visual, frontoparietal, somatomotor networks. Hub overlapped highly groups. Age negatively correlated Our findings demonstrate alterations homosexual males stage. Frontal may be important finding HIV-associated disorder.

Language: Английский

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