Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 226, P. 1 - 12
Published: Nov. 8, 2024
Language: Английский
Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 428 - 446
Published: Feb. 7, 2024
Language: Английский
Citations
29
Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102689 - 102689
Published: April 1, 2023
This study was focused on exploring the role of HIV-1 Tat protein in mediating microglial ferroptosis. Exposure mouse primary cells (mPMs) to resulted induction ferroptosis, which characterized by increased expression Acyl-CoA synthetase long-chain family member 4 (ACSL4), turn, leading generation oxidized phosphatidylethanolamine, elevated levels lipid peroxidation, upregulated labile iron pool (LIP) and ferritin heavy chain-1 (FTH1), decreased glutathione peroxidase-4 mitochondrial outer membrane rupture. Also, inhibition ferroptosis ferrostatin-1 (Fer-1) or deferoxamine (DFO) treatment suppressed ferroptosis-related changes mPMs. Similarly, knockdown ACSL4 gene silencing also inhibited induced Tat. Furthermore, peroxidation release proinflammatory cytokines, such as TNFα, IL6, IL1β activation. Pretreatment mPMs with Fer-1 DFO further blocked Tat-mediated activation vitro reduced cytokines. We identified miR-204 an upstream modulator ACSL4, downregulated exposed Transient transfection mimics while inhibiting These findings were validated transgenic rats well HIV + ve human brain samples. Overall, this underscores a novel mechanism(s) underlying involving miR-204-ACSL4 signaling.
Language: Английский
Citations
37
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
Citations
25
Burns & Trauma, Journal Year: 2024, Volume and Issue: 12
Published: Jan. 1, 2024
Abstract Extracellular vesicles (EVs) are heterogeneous membrane-like secreted by living cells that involved in many physiological and pathological processes act as intermediaries of intercellular communication molecular transfer. Recent studies have shown EVs from specific sources regulate tissue repair regeneration delivering proteins, lipids, nucleic acids to target signaling molecules. Nanotechnology breakthroughs facilitated the development exploration engineered for repair. Enhancements through gene editing, surface modification, content modification further improved their therapeutic efficacy. This review summarizes potential regeneration, mechanisms action, research progress regenerative medicine. highlights design logic typical examples explores prospects The aim this is provide new insights into applications, thereby expanding use
Language: Английский
Citations
10
Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18
Published: March 5, 2024
Background Some evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors the endocannabinoid system in Tat transgenic mice. Methods mice (female/male) were injected with (3, 10, 30 mg/kg) assessed for antinociception, activity, coordination, anxiety-like behavior, recognition memory. Brains taken quantify endocannabinoids, cannabinoid receptors, catabolic enzymes. Additionally, metabolite 7-hydroxy-CBD quantified plasma cortex. Results decreased supraspinal-related nociception locomotion. sex had little no any of behavioral measures. For male was associated elevated concentration proinflammatory arachidonic acid CNS regions, including cerebellum also showed higher FAAH expression levels Tat(+) males. GPR55 striatum females compared metabolism altered by expression. Conclusion Findings indicate are not Tat, minimal behavior system.
Language: Английский
Citations
6
Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(4)
Published: April 1, 2024
Abstract Our previous findings demonstrated that astrocytic HIF‐1α plays a major role in HIV‐1 Tat‐mediated amyloidosis which can lead to Alzheimer's‐like pathology‐a comorbidity of HIV‐Associated Neurocognitive Disorders (HAND). These amyloids be shuttled extracellular vesicles, and we sought assess whether Tat stimulated astrocyte‐derived EVs (ADEVs) containing the toxic could result neuronal injury vitro vivo. We thus hypothesized blocking likely mitigate Tat‐ADEV‐mediated injury. Rat hippocampal neurons when exposed Tat‐ADEVs carrying exhibited amyloid accumulation synaptodendritic injury, leading functional loss as evidenced by alterations miniature excitatory post synaptic currents. The silencing not only reduced biogenesis ADEVs, well cargos, but also ameliorated synaptodegeneration. Next, determined effect hippocampus naive mice brains. Naive receiving Tat‐ADEVs, behavioural changes, Alzheimer's ’s‐like pathology accompanied This impairment(s) was observed injected with silenced ADEVs. is first report demonstrating amyloid‐carrying ADEVs mediating synaptodegeneration changes associated HAND highlights protective HIF‐1α.
Language: Английский
Citations
6
ASN NEURO, Journal Year: 2025, Volume and Issue: 17(1)
Published: Jan. 13, 2025
People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting a co-receptor for viral entry into CD4+ cells. Notably, CCR5 has been implicated cognition unrelated infection. Inhibition shown improve learning memory. To test whether involved cognitive changes HAND, we used non-infectious, transgenic model which Tat inducibly expressed. Well-powered cohorts male female mice were placed on diet containing doxycycline induce expression 8-wks. Males showed Tat-mediated deficits Barnes maze spatial memory; females no impairments. Deficits males fully reversed by antagonist, maraviroc (MVC). not found novel object recognition or contextual fear conditioning either sex. Based earlier work, hypothesized that MVC might increase brain-derived neurotrophic factor (BDNF), essential maintaining synaptodendritic function. did mBDNF proBDNF ratio males, perhaps contributing improved cognition.
Language: Английский
Citations
0
Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown
Published: March 12, 2025
Extracellular vesicles (EVs) convey complex signals between cells that can be used to promote neuronal plasticity and neurological recovery in brain disease models. These EV are multimodal context-dependent, making them unique therapeutic principles. This review analyzes how EVs released from various cell sources control metabolic function, survival plasticity. Preferential sites of communication the interfaces pre- postsynaptic neurons at synapses, astrocytes plasma membranes or tripartite oligodendrocytes axons, microglial cells/macrophages neurons, cerebral microvascular neurons. At each these interfaces, support mitochondrial function metabolism under physiological conditions orchestrate response injury. In injured brain, promotion by is tightly linked with actions on metabolism, oxidative stress immune responses. Via stabilization balance, responses activated functional induced. As such, lay ground for
Language: Английский
Citations
0
Current Opinion in Physiology, Journal Year: 2025, Volume and Issue: unknown, P. 100826 - 100826
Published: March 1, 2025
Language: Английский
Citations
0
Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10
Published: May 17, 2023
Emerging evidence suggests that brain derived extracellular vesicles (EVs) and particles (EPs) can cross blood-brain barrier mediate communication among neurons, astrocytes, microglial, other cells of the central nervous system (CNS). Yet, a complete understanding molecular landscape function circulating EVs & EPs (EVPs) remain major gap in knowledge. This is mainly due to lack technologies isolate separate all EVPs heterogeneous dimensions low buoyant density. In this review, we aim provide comprehensive neurosecretome, including carry signature both its microenvironment systemic circulation. We discuss biogenesis EVPs, their function, cell-to-cell communication, past emerging isolation technologies, therapeutics, liquid-biopsy applications. It important highlight constant state evolution; hence, not only literature current but also speculate as how novel may contribute etiology addiction, depression, psychiatric, neurodegenerative diseases, aid real time monitoring "living brain". Overall, neurosecretome concept introduce here embody compendium for disease pathogenesis. Finally, purpose inclusion particles, have used term defined by International Society Extracellular Vesicles (ISEV).
Language: Английский
Citations
8