Healthy ageing and longevity, Journal Year: 2024, Volume and Issue: unknown, P. 119 - 142
Published: Jan. 1, 2024
Language: Английский
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 18, 2025
HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, mechanisms allowing HIV-1 entry replication central nervous system (CNS) are poorly understood. Here, we show that α-synuclein (to lesser extent) Aβ fibrils associated with neurological diseases enhance human T cells, macrophages, microglia. Additionally, an Env-derived amyloidogenic peptide accelerated amyloid formation by peptides. Mechanistic studies interact particles promote virion attachment fusion target cells. overall negative surface charge, these facilitate interactions between cellular membranes. The enhancing effects of extracts on infection correlated binding to Thioflavin T, dye commonly used stain amyloids. Our results suggest detrimental interplay amyloids may contribute development neurodegenerative diseases.
Language: Английский
Citations
2
Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11
Published: Jan. 7, 2025
Human immunodeficiency virus (HIV) infection is the cause of acquired syndrome (AIDS). Combination antiretroviral therapy (cART) has successfully controlled AIDS, but HIV-associated neurocognitive disorders (HANDs) remain prevalent among people with HIV. HIV often associated substance use, which promotes transmission and viral replication exacerbates HANDs even in era cART. Thus, comorbid effects use exacerbate neuropathogenesis HANDs. Unraveling mechanism(s) this exacerbation at molecular, cell-type, brain region levels may provide a better understanding HAND persistence. This review aims to highlight specific regions cell types involved persistence includes an overview post-translational modifications, alterations microglia-specific biomarkers, possible mechanistic pathways that link epigenomic modifications functional protein microglia. The impairment microglial proteins are neural circuit function appears contribute breakdown cellular communication neurodegeneration epigenetic modification N-terminal acetylation currently understudied, discussed brief demonstrate important role infected microglia within regions. discussion also explores whether combined effective preventing or substance-use-mediated
Language: Английский
Citations
1
Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(8), P. 8852 - 8873
Published: Aug. 14, 2024
Reactive oxygen species (ROS) are widely regarded as signaling molecules and play essential roles in various cellular processes, but when present excess, they can lead to oxidative stress (OS). Growing evidence suggests that the OS plays a critical role pathogenesis of HIV infection is associated with several comorbidities HIV-infected individuals. ROS, generated both naturally during mitochondrial metabolism response trigger host antiviral responses also promote viral replication. While multifaceted ROS pathophysiology clearly need more investigation, this review paper unravels mechanisms generation context infections, offering insights into protein-mediated antiretroviral therapy-generated OS. Though protein Tat significantly attributed endogenous increase post infection, sums up contribution other proteins HIV-mediated elicitation ROS. Given investigations recognizing significant onset progression diverse pathologies, explores function mediation an array pathologies retroviral therapy. patients observed disruption antioxidant defense system, therapy gaining focus potential therapeutic intervention well discussed. scenario, further exploratory studies imperative identifying alternative strategies could mitigate toxicities ART-induced
Language: Английский
Citations
7
Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(6), P. 1631 - 1631
Published: March 13, 2024
Background: Human Immunodeficiency Virus (HIV) infection represents a significant public health concern and, consequently, the incidence of HIV-Associated Neurocognitive Disorder (HAND) has grown over years. The present study aims to assess HAND with Montreal Cognitive Assessment (MoCA) in People Living With HIV/AIDS (PLWHA) find associations cognitive impairment. Methods: included 210 PLWHA, aged from 30 81 years, whom, 137 (65.2%) were males. They assessed at Immunology Service University Hospital Monserrato, Cagliari, Italy, between November 2022 and April 2023. Results: sample showed an overall optimal response antiretroviral therapy, as shown by excellent levels CD4+ lymphocytes HIV RNA copies. A sum 115 subjects (54.8%) considered cognitively impaired multivariate analysis demonstrated that it was independently associated duration (OR: 0.96), age 1.12), alanine aminotransferase (ALT) 1.02), depression 1.33). By dichotomizing variables, significance association confirmed for (65-year threshold) (χ2: 5.142, p = 0.0233) 7.834, 0.0051). Conclusions: Our demonstrates is hard both statistically clinically significantly variables impairment strongest independent depressed mood.
Language: Английский
Citations
5
Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(11), P. 1076 - 1089
Published: July 1, 2024
Language: Английский
Citations
5
PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(9), P. e1012168 - e1012168
Published: Sept. 16, 2024
Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, influence central nervous system (CNS) cannot be overlooked. Within brain, microglia and CNS-associated macrophages (CAMs) serve as primary targets simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects establish a viral reservoir. Given gaps our understanding of how these cells respond vivo acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) myeloid from brains three rhesus macaques 12 days after SIV along with uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated activated expressing high levels inflammatory disease-related molecules. In response population decreased, while increased. All exhibited upregulation MHC class I molecules interferon-related genes, indicating their crucial roles defending against during phase. also upregulated genes linked cellular senescence. Additionally, identified two CAM populations: CD14 low CD16 hi CAMs. Interestingly, dominant changed one an phenotype. Specific within macrophage cluster were associated neurodegenerative pathways, suggesting potential links neurocognitive disorders. research sheds light intricate interactions between innate responses, CNS, providing valuable insights future investigations.
Language: Английский
Citations
5
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 8, 2025
Abstract HIV infection exerts profound and long-lasting neurodegenerative effects on the central nervous system (CNS) that can persist despite antiretroviral therapy (ART). Here, we used single-nucleus multiome sequencing to map transcriptomic epigenetic landscapes of postmortem human brains from 13 healthy individuals 20 with who have a history treatment ART. Our study spanned three distinct regions—the prefrontal cortex, insular ventral striatum—enabling comprehensive exploration region-specific cross-regional perturbations. We found widespread persistent HIV-associated transcriptional alterations across multiple cell types. Detailed analyses microglia revealed state changes marked by immune activation metabolic dysregulation, while integrative multiomic profiling astrocytes identified subpopulations, including reactive subpopulation unique HIV-infected brains. These findings suggest cells people exhibit molecular shifts may underlie ongoing neuroinflammation CNS dysfunction. Furthermore, cell–cell communication uncovered dysregulated pro-inflammatory interactions among glial populations, underscoring multifaceted enduring impact brain milieu. Collectively, our atlas reveals states signatures signaling providing framework for developing targeted therapies neurological
Language: Английский
Citations
0
AIDS Research and Therapy, Journal Year: 2025, Volume and Issue: 22(1)
Published: Feb. 6, 2025
Language: Английский
Citations
0
Current Opinion in HIV and AIDS, Journal Year: 2025, Volume and Issue: unknown
Published: March 4, 2025
The neuropathogenesis of acute HIV leads to rapid central nervous system (CNS) involvement, characterized by early viral entry, immune activation, and the formation reservoirs. Despite effective antiretroviral therapy (ART), these reservoirs persist, drive neuroinflammation injury lead HIV-associated neurodegenerative disorders (HAND). This review provides an updated synthesis mechanisms in neuropathogenesis, biomarkers CNS emerging therapeutic approaches. A deeper understanding is critical for addressing persistent HAND ART-treated individuals. Growing evidence now supports principal role infected CD4+ T cells mediating neuroinvasion alongside monocytes, resulting seeding perivascular macrophages, pericytes, adjacent microglia astrocytes. These contribute ongoing transcriptional activity persistence despite therapy. Neuroinflammation, driven activated microglia, astrocytes, inflammasomes, neurotoxic proteins, disrupts neuronal homeostasis. Emerging therapies, including latency-reversing agents transcription inhibitors, show promise reducing reservoir activity. Understanding has significant implications developing targeted therapies mitigate HAND. Strategies eliminate reduce should be prioritized improve long-term cognitive outcomes people with HIV.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: April 4, 2024
ABSTRACT Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, influence central nervous system (CNS) cannot be overlooked. Within brain, microglia and CNS-associated macrophages (CAMs) serve as primary targets HIV, well simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects establishment of a viral reservoir. Given gaps our understanding how these cells respond vivo acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) myeloid from brains three rhesus macaques 12-days after SIV along with uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated activated expressing high levels inflammatory disease-related molecules. In response population decreased, while increased. All exhibited upregulation MHC class I molecules interferon-related genes, indicating their crucial roles defending against during phase. also upregulated genes linked cellular senescence. Additionally, identified two CAM populations: CD14 low CD16 hi CAMs. Interestingly, dominant changed one an phenotype. Notably, specific within macrophage cluster were associated neurodegenerative pathways, suggesting potential links neurocognitive disorders. research sheds light intricate interactions between innate responses, CNS, providing valuable insights future investigations. AUTHOR SUMMARY HIV’s entry into dysfunction, HIV-associated disorders (HAND), While are responses remain poorly defined. To address this, employed scRNA-seq technique study populations infection. By identifying signature different phenotypes mapping them various biological pathological discovered cell strongly other varying degrees activation among possibly mediated by signaling pathways. developed signs senescence pathway. These findings shed immunological brain therapeutic strategies targeting this critical stage aiming eliminate
Language: Английский
Citations
2