HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology DOI Open Access

Landon John-Patrick Thompson,

Jessica Genovese,

Zhenzi Hong

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4697 - 4697

Published: April 25, 2024

Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with continue experience HIV-associated neurocognitive disorder (HAND). HAND is associated impairment, including motor and memory loss. has been detected brain within 8 days of estimated exposure mechanisms for this early entry are being actively studied. Once having entered into central nervous system (CNS), degrades blood-brain barrier through production its gp120 Tat proteins. These proteins directly toxic endothelial cells neurons, propagate inflammatory cytokines by activation immune dysregulation tight junction The BBB breakdown progression disease. One main hurdles treatment latent pool cells, which insensitive cART prolong inflammation harboring provirus long-lived that can reactivate, causing damage. Multiple strategies studied combat HAND; however, clinically, these approaches have insufficient require further revisions. goal paper aggregate known challenges HAND.

Language: Английский

Precision drug delivery to the central nervous system using engineered nanoparticles DOI
Jingjing Gao, Ziting Xia,

Swetharajan Gunasekar

et al.

Nature Reviews Materials, Journal Year: 2024, Volume and Issue: 9(8), P. 567 - 588

Published: June 25, 2024

Language: Английский

Citations

27
The duality of amyloid-β: its role in normal and Alzheimer’s disease states DOI Creative Commons
Ali Azargoonjahromi

Molecular Brain, Journal Year: 2024, Volume and Issue: 17(1)

Published: July 17, 2024

Abstract Alzheimer’s disease (AD) is a degenerative neurological condition that gradually impairs cognitive abilities, disrupts memory retention, and impedes daily functioning by impacting the cells of brain. A key characteristic AD accumulation amyloid-beta (Aβ) plaques, which play pivotal roles in progression. These plaques initiate cascade events including neuroinflammation, synaptic dysfunction, tau pathology, oxidative stress, impaired protein clearance, mitochondrial disrupted calcium homeostasis. Aβ also closely associated with other hallmark features AD, underscoring its significance. generated through cleavage amyloid precursor (APP) plays dual role depending on processing pathway. The non-amyloidogenic pathway reduces production has neuroprotective anti-inflammatory effects, whereas amyloidogenic leads to peptides, Aβ40 Aβ42, contribute neurodegeneration toxic effects AD. Understanding multifaceted Aβ, particularly crucial for developing effective therapeutic strategies target metabolism, aggregation, clearance aim mitigating detrimental consequences disease. This review aims explore mechanisms functions under normal abnormal conditions, examining both beneficial effects.

Language: Английский

Citations

21
Microglial activation states and their implications for Alzheimer's Disease DOI Creative Commons

Zachary Valiukas,

Kathy Tangalakis, Vasso Apostolopoulos

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: 12(1), P. 100013 - 100013

Published: Jan. 1, 2025

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) tau protein in brain. Microglia, key immune cells central nervous system, play an important role AD development progression, primarily through their responses to Aβ NFTs. Initially, microglia can clear Aβ, but AD, activation overwhelms protective mechanisms, leading sustained neuroinflammation that enhances plaque toxicity, setting off damaging cycle affects neurons, astrocytes, cerebral vasculature, other microglia. Current treatments have been largely ineffective, though emerging immunotherapies focusing on removal show promise, often overlook neuroinflammation. Activated display complex range phenotypes be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe significant overlap between states. strongly induce inflammatory activity, triggering production reactive oxygen species, cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, impaired clearance. These processes contribute neural tissue loss, manifesting as cognitive decline such executive function memory. Conversely, exerts neuroprotective effects suppressing pathways releasing neurotrophic factors aid neuron repair protection. Induction states may offer dual therapeutic approach address both AD. This suggests potential strategies modulate microglial phenotypes, aiming restore functions mitigate disease progression simultaneously targeting inflammation pathology.

Language: Английский

Citations

4
The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder DOI Creative Commons
Sheetal Sreeram, Fengchun Ye, Yoelvis García‐Mesa

et al.

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

Citations

52
Microglia-Astrocyte Communication in Alzheimer’s Disease DOI Creative Commons
Yingying Wu, Ulrich Eisel

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(3), P. 785 - 803

Published: Aug. 25, 2023

Microglia and astrocytes are regarded as active participants in the central nervous system under various neuropathological conditions, including Alzheimer's disease (AD). Both microglia astrocyte activation have been reported to occur with a spatially temporarily distinct pattern. Acting double-edged sword, glia-mediated neuroinflammation may be both detrimental beneficial brain. In variety of neuropathologies, activated before astrocytes, which facilitates activation. Yet reactive can also prevent adjacent addition helping them become activated. Studies describe changes genetic profile well cellular molecular responses these two types glial cells that contribute dysfunctional immune crosstalk AD. this paper, we construct current knowledge microglia-astrocyte communication, highlighting multifaceted functions their role A thorough comprehension communication could hasten creation novel AD treatment approaches.

Language: Английский

Citations

38
Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases DOI Open Access
Mari Gotoh, Yasunori Miyamoto,

Hiroko Ikeshima‐Kataoka

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1599 - 1599

Published: Jan. 13, 2023

Both astrocytic and microglial functions have been extensively investigated in healthy subjects neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes extracellular matrix interactions between reactive microglia normal states diseases, because authors feel it necessary to elucidate mechanisms among activated glial cells pathology neurological diseases order pave way for drug discovery. Finally, will cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces variety biological activities brain both vivo vitro. We propose cPA may serve as novel therapeutic molecule treatment injury neuroinflammation.

Language: Английский

Citations

23
Oxidative stress and inflammation cause auditory system damage via glial cell activation and dysregulated expression of gap junction proteins in an experimental model of styrene-induced oto/neurotoxicity DOI Creative Commons
Fabiola Paciello, Anna Pisani, Rolando Rolesi

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 4, 2024

Abstract Background Redox imbalance and inflammation have been proposed as the principal mechanisms of damage in auditory system, resulting functional alterations hearing loss. Microglia astrocytes play a crucial role mediating oxidative/inflammatory injury central nervous system; however, glial cells is still elusive. Objectives Here we investigated glial-mediated responses to toxic peripheral structures pathway, i.e., cochlea cortex (ACx), rats exposed styrene, volatile compound with well-known oto/neurotoxic properties. Methods Male adult Wistar were treated styrene (400 mg/kg daily for 3 weeks, 5/days week). Electrophysiological, morphological, immunofluorescence molecular analyses performed both ACx evaluate underlying styrene-induced oto/neurotoxicity system. Results We showed that insult induced by increases oxidative stress ACx. This was associated macrophages cell activation, increased expression inflammatory markers (i.e., pro-inflammatory cytokines chemokine receptors) connexin (Cxs) pannexin (Panx) expression, likely responsible dysregulation microglia/astrocyte network. Specifically, found downregulation Cx26 Cx30 cochlea, high level Cx43 Panx1 Conclusions Collectively, our results provide novel evidence on immune activation system at levels, also involving gap junction networks. Our data suggest targeting connexin/pannexin might be useful attenuate

Language: Английский

Citations

15
Oxidative stress–mediated neuroinflammation in Alzheimer’s disease DOI

Sayed Mohammed Firdous,

Sahabaj Ali Khan, Amritangshu Maity

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Language: Английский

Citations

15
Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction DOI Creative Commons
Yousef Tizabi, Bruk Getachew, Sheketha R. Hauser

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558

Published: May 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Language: Английский

Citations

13
Neuroinflammaging: A Tight Line Between Normal Aging and Age-Related Neurodegenerative Disorders DOI Creative Commons
Luca Soraci, Andrea Corsonello, Ersilia Paparazzo

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Aging in the healthy brain is characterized by a low-grade, chronic, and sterile inflammatory process known as neuroinflammaging. This condition, mainly consisting an up-regulation of response at level, contributes to pathogenesis age-related neurodegenerative disorders. Development this proinflammatory state involves interaction between genetic environmental factors, able induce epigenetic modifications. Indeed, exposure compounds, drugs, infections, can contribute modifications DNA methylome, histone fold proteins, nucleosome positioning, leading modulation neuroinflammatory responses. Furthermore, some modifiers, which combine interact during life course, modeling epigenome dynamics sustain, or dampen phenotype. The aim review summarize current knowledge about neuroinflammaging with particular focus on mechanisms underlying onset progression cascades central nervous system; furthermore, we describe diagnostic biomarkers that may increase accuracy help tailor therapeutic strategies patients diseases.

Language: Английский

Citations

11