ArticleThe American journal of pathology2010
Long-term expression of tissue-inhibitor of matrix metalloproteinase-1 in the murine central nervous system does not alter the morphological and behavioral phenotype but alleviates the course of experimental allergic encephalomyelitis.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- The Preventive Effect of Ulinastatin on Blood-Brain Barrier Dysfunction in Rats with Postoperative Cognitive Dysfunction After General Anaesthesia with Isoflurane.International journal of molecular sciences · 2024Article
- 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
- Review
- Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.International journal of molecular sciences · 2021Review
- Neoplastic Cells are the Major Source of MT-MMPs inCancers · 2020Article
- TIMP1 preserves the blood-brain barrier through interacting with CD63/integrinActa pharmaceutica Sinica. B · 2020Article
- TIMP-1 Promotes Oligodendrocyte Differentiation Through Receptor-Mediated Signaling.Molecular neurobiology · 2019Article
- Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.PloS one · 2016Article
- Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases.Mediators of inflammation · 2015Review
- MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis.ASN neuro · 2013Article
- Article
- Article
- Tissue inhibitor of metalloproteinases-1 protects human neurons from staurosporine and HIV-1-induced apoptosis: mechanisms and relevance to HIV-1-associated dementia.Cell death & disease · 2012Article
- A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli.Journal of neuroinflammation · 2011Article
- Astrocytic tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes oligodendrocyte differentiation and enhances CNS myelination.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- T-cell production of matrix metalloproteinases and inhibition of parasite clearance by TIMP-1 during chronic Toxoplasma infection in the brain.ASN neuro · 2011Article
- Matrix metalloproteinases, synaptic injury, and multiple sclerosis.Frontiers in psychiatry · 2010Article
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitors of metalloproteinases (TIMPs) are a family of closely related proteins that inhibit matrix metalloproteinases (MMPs). In the central nervous system (CNS), TIMPs 2, 3, and 4 are constitutively expressed at high levels, whereas TIMP1 can be induced by various stimuli. Here, we studied the effects of constitutive expression of TIMP1 in the CNS in transgenic mice. Transgene expression started prenatally and persisted throughout lifetime at high levels. Since MMP activity has been implicated in CNS development, in proper function of the adult CNS, and in inflammatory disorders, we investigated Timp1-induced CNS alterations. Despite sufficient MMP inhibition, high expressor transgenic mice had a normal phenotype. The absence of compensatory up-regulation of MMP genes in the CNS of Timp1 transgenic mice indicates that development, learning, and memory functions do not require the entire MMP arsenal. To elucidate the effects of strong Timp1 expression in CNS inflammation, we induced experimental allergic encephalomyelitis. We observed a Timp1 dose-dependent mitigation of both experimental allergic encephalomyelitis symptoms and histological lesions in the CNS of transgenic mice. All in all, our data demonstrate that (1) long-term CNS expression of TIMP1 with complete suppression of gelatinolytic activity does not interfere with physiological brain function and (2) TIMP1 might constitute a promising candidate for long-term therapeutic treatment of inflammatory CNS diseases such as multiple sclerosis.
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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.