ArticleCell death & disease2012
Tissue inhibitor of metalloproteinases-1 protects human neurons from staurosporine and HIV-1-induced apoptosis: mechanisms and relevance to HIV-1-associated dementia.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 50 citations in OpenAlex.
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- Mitochondrial dysfunction as a key player in aggravating periodontitis among diabetic patients: review of the current scope of knowledge.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Exploring DNA methylation age and the influence of physical performance, and hypertension on frailty in elderly women.Scientific reports · 2025Article
- Downregulation of STAT3 transcription factor reverses synaptotoxic phenotype of reactive astrocytes associated with prion diseases.Acta neuropathologica communications · 2025Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Expression of Matrix Metalloproteinases in the Circulating Immune Cells in Children withInternational journal of molecular sciences · 2023Article
- DNA methylation GrimAge version 2.Aging · 2022Article
- Adipose stem cell-derived extracellular vesicles ameliorates corticosterone-induced apoptosis in the cortical neurons via inhibition of ER stress.Stem cell research & therapy · 2022Article
- Autologous treatment for ALS with implication for broad neuroprotection.Translational neurodegeneration · 2022Article
- Neuroinflammatory astrocyte subtypes in the mouse brain.Nature neuroscience · 2021Article
- A DNA methylation clock associated with age-related illnesses and mortality is accelerated in men with combat PTSD.Molecular psychiatry · 2021Article
- Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Bioinformatic analysis identifies key transcriptome signatures in temporal lobe epilepsy.CNS neuroscience & therapeutics · 2020Article
- Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV.Journal of neurovirology · 2020Article
- Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
HIV-1-associated dementia (HAD)-relevant proinflammatory cytokines robustly induce astrocyte tissue inhibitor of metalloproteinases-1 (TIMP-1). As TIMP-1 displays pleotropic functions, we hypothesized that TIMP-1 expression may serve as a neuroprotective response of astrocytes. Previously, we reported that chronically activated astrocytes fail to maintain elevated TIMP-1 expression, and TIMP-1 levels are lower in the brain of HAD patients; a phenomenon that may contribute to central nervous system pathogenesis. Further, the role of TIMP-1 as a neurotrophic factor is incompletely understood. In this study, we report that staurosporine (STS) and HIV-1(ADA) virus, both led to induction of apoptosis in cultured primary human neurons. Interestingly, cotreatment with TIMP-1 protects neurons from apoptosis and reverses neuronal morphological changes induced by these toxins. Further, the anti-apoptotic effect was not observed with TIMP-2 or -3, but was retained in a mutant of the N-terminal TIMP-1 protein with threonine-2 mutated to glycine (T2G) that is deficient in matrix metalloproteinase (MMP)-1, -2 and -3 inhibitory activity. Therefore, the mechanism is specific to TIMP-1 and partially independent of MMP-inhibition. Additionally, TIMP-1 modulates the Bcl-2 family of proteins and inhibits opening of mitochondrial permeability transition pores induced by HIV-1 or STS. Together, these findings describe a novel function, mechanism and direct role of TIMP-1 in neuroprotection, suggesting its therapeutic potential in HAD and possibly in other neurodegenerative diseases.
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