ReviewCurrent HIV research2015
Mechanisms of HIV-1 Tat neurotoxicity via CDK5 translocation and hyper-activation: role in HIV-associated neurocognitive disorders.
Review in Current HIV research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 56 citations in OpenAlex.
- Host Genetic Regulation of NLRP3 Inflammasome Cytokines Reveals Immune and Vascular Pathways in HIV.medRxiv : the preprint server for health sciences · 2026Article
- Review
- DNA Methylation Regulates CDK5R1 and NRBP1 to Exert Effects on Alcohol Dependence: Insights From Mendelian Randomization.Addiction biology · 2026Article
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Genotoxic consequences of viral infections.Npj viruses · 2025Review
- The potential emerging role of piRNA/PIWI complex in virus infection.Virus genes · 2024Review
- HIV-1 gp120 Protein Activates Cyclin-Dependent Kinase 1, a Possible Link to Central Nervous System Cell Death.Viruses · 2022Article
- HIV-1 Tat and cocaine coexposure impacts piRNAs to affect astrocyte energy metabolism.Epigenomics · 2022Article
- Caloric Restriction Mimetic 2-Deoxyglucose Reduces Inflammatory Signaling in Human Astrocytes: Implications for Therapeutic Strategies Targeting Neurodegenerative Diseases.Brain sciences · 2022Article
- Three decades of Cdk5.Journal of biomedical science · 2021Review
- HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation.Genomics · 2021Article
- HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation.Epigenetics · 2021Article
- PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke.International journal of molecular sciences · 2021Article
- HIV-1 and drug abuse comorbidity: Lessons learned from the animal models of NeuroHIV.Neuroscience letters · 2021Review
- Morphine and HIV-1 Tat interact to cause region-specific hyperphosphorylation of tau in transgenic mice.Neuroscience letters · 2021Article
- Inflammation-induced PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons.Translational neurodegeneration · 2020Article
- Beta amyloid levels in cerebrospinal fluid of HIV-infected people vary by exposure to antiretroviral therapy.AIDS (London, England) · 2020Article
- Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorder.Journal of neuroinflammation · 2020Article
- Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance.Advances in experimental medicine and biology · 2020Review
- HIV-1 Tat: Role in Bystander Toxicity.Frontiers in cellular and infection microbiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The advent of more effective antiretroviral therapies has reduced the frequency of HIV dementia, however the prevalence of milder HIV associated neurocognitive disorders [HAND] is actually rising. Neurodegenerative mechanisms in HAND might include toxicity by secreted HIV-1 proteins such as Tat, gp120 and Nef that could activate neuro-inflammatory pathways, block autophagy, promote excitotoxicity, oxidative stress, mitochondrial dysfunction and dysregulation of signaling pathways. Recent studies have shown that Tat could interfere with several signal transduction mechanisms involved in cytoskeletal regulation, cell survival and cell cycle re-entry. Among them, Tat has been shown to hyper-activate cyclin-dependent kinase [CDK] 5, a member of the Ser/Thr CDKs involved in cell migration, angiogenesis, neurogenesis and synaptic plasticity. CDK5 is activated by binding to its regulatory subunit, p35 or p39. For this manuscript we review evidence showing that Tat, via calcium dysregulation, promotes calpain-1 cleavage of p35 to p25, which in turn hyper-activates CDK5 resulting in abnormal phosphorylation of downstream targets such as Tau, collapsin response mediator protein-2 [CRMP2], doublecortin [DCX] and MEF2. We also present new data showing that Tat interferes with the trafficking of CDK5 between the nucleus and cytoplasm. This results in prolonged presence of CDK5 in the cytoplasm leading to accumulation of aberrantly phosphorylated cytoplasmic targets [e.g.: Tau, CRMP2, DCX] that impair neuronal function and eventually lead to cell death. Novel therapeutic approaches with compounds that block Tat mediated hyper-activation of CDK5 might be of value in the management of HAND.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.