ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2015
Interaction of paroxetine with mitochondrial proteins mediates neuroprotection.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial.Journal of neurovirology · 2018Trial
- The selective serotonin reuptake inhibitor paroxetine improves right ventricular systolic function in experimental pulmonary hypertension.Journal of molecular and cellular cardiology plus · 2024Article
- Accelerated neurodegeneration of basal forebrain cholinergic neurons in HIV-1 gp120 transgenic mice: Critical role of the p75 neurotrophin receptor.Brain, behavior, and immunity · 2024Article
- Neurotoxic properties of the Zika virus envelope protein.Experimental neurology · 2023Article
- Cognitive Health in Persons With Human Immunodeficiency Virus: The Impact of Early Treatment, Comorbidities, and Aging.The Journal of infectious diseases · 2023Article
- An Overview: The Diversified Role of Mitochondria in Cancer Metabolism.International journal of biological sciences · 2023Review
- A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment.Microorganisms · 2022Review
- Crucial Role of Central Nervous System as a Viral Anatomical Compartment for HIV-1 Infection.Microorganisms · 2021Review
- Protective effects of antidepressant citalopram against abnormal APP processing and amyloid beta-induced mitochondrial dynamics, biogenesis, mitophagy and synaptic toxicities in Alzheimer's disease.Human molecular genetics · 2021Article
- Methamphetamine and Cannabis: A Tale of Two Drugs and their Effects on HIV, Brain, and Behavior.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Fungal Translocation: A Driving Force Behind the Occurrence of Non-AIDS Events?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- HIV-associated neurodegeneration: exploitation of the neuronal cytoskeleton.Journal of neurovirology · 2019Review
- The Synergistic Combination of Everolimus and Paroxetine Exerts Post-ischemic Neuroprotection In Vitro.Cellular and molecular neurobiology · 2018Article
- Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research.Journal of neurovirology · 2018Review
- Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes.Oncotarget · 2017Article
- Conditional Human Immunodeficiency Virus Transactivator of Transcription Protein Expression Induces Depression-like Effects and Oxidative Stress.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2017Article
- Striatal magnetic resonance spectroscopy abnormalities in young adult SAPAP3 knockout mice.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2016Article
- Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms.Frontiers in psychiatry · 2015Review
Corrections and comments
- Erratum issuedErratum to: Interaction of Paroxetine with Mitochondrial Proteins Mediates Neuroprotection.2016 · Wang, Tonguang [Corrected to Wang, Tongguang]
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
There are severe neurological complications that arise from HIV infection, ranging from peripheral sensory neuropathy to cognitive decline and dementia for which no specific treatments are available. The HIV proteins secreted from infected macrophages, gp120 and Tat, are neurotoxic. The goal of this study was to screen, identify and develop neuroprotective compounds relevant to HIV-associated neurocognitive disorders (HAND). We screened more than 2000 compounds that included FDA approved drugs for protective efficacy against oxidative stress-mediated neurodegeneration and identified selective serotonin reuptake inhibitors (SSRIs) as potential neuroprotectants. Numerous SSRIs were then extensively evaluated as protectants against neurotoxicity as measured by changes in neuronal cell death, mitochondrial potential, and axodendritic degeneration elicited by HIV Tat and gp120 and other mitochondrial toxins. While many SSRIs demonstrated neuroprotective actions, paroxetine was potently neuroprotective (100 nM potency) against these toxins in vitro and in vivo following systemic administration in a gp120 neurotoxicity model. Interestingly, the inhibition of serotonin reuptake by paroxetine was not required for neuroprotection, since depletion of the serotonin transporter had no effect on its neuroprotective properties. We determined that paroxetine interacts selectively and preferentially with brain mitochondrial proteins and blocks calcium-dependent swelling but had less effect on liver mitochondria. Additionally, paroxetine induced proliferation of neural progenitor cells in vitro and in vivo in gp120 transgenic animals. Therefore, SSRIs such as paroxetine may provide a novel adjunctive neuroprotective and neuroregenerative therapy to treat HIV-infected individuals.
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Registered trials
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.