دورية أكاديمية
أعرض في EDS

The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain.

التفاصيل البيبلوغرافية
العنوان: The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain.
المؤلفون: Dewing JM; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK., Carare RO; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK., Lotery AJ; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK.; Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK., Ratnayaka JA; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK.
المصدر: Cells [Cells] 2019 Dec 21; Vol. 9 (1). Date of Electronic Publication: 2019 Dec 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Review
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Brain Diseases/*metabolism , Neurodegenerative Diseases/*metabolism , Retinal Diseases/*metabolism , Tissue Inhibitor of Metalloproteinase-3/*metabolism, Animals ; Brain Diseases/genetics ; Brain Diseases/pathology ; Extracellular Matrix/metabolism ; Humans ; Mutation ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/pathology ; Retinal Diseases/genetics ; Retinal Diseases/pathology
مستخلص: Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degeneration (AMD) and Sorsby fundus dystrophy, and potentially, through indirect mechanisms, with Alzheimer's disease. Insights into TIMP-3 activities may be gleaned from studying Sorsby-linked mutations. However, recent findings do not fully support the prevailing hypothesis that a gain of function through the dimerisation of mutated TIMP-3 is responsible for retinopathy. Findings from Alzheimer's patients suggest a hitherto poorly studied relationship between TIMP-3 and the Alzheimer's-linked amyloid-beta (A) proteins that warrant further scrutiny. This may also have implications for understanding AMD as aged/diseased retinae contain high levels of A. Findings from TIMP-3 knockout and mutant knock-in mice have not led to new treatments, particularly as the latter does not satisfactorily recapitulate the Sorsby phenotype. However, recent advances in stem cell and in vitro approaches offer novel insights into understanding TIMP-3 pathology in the retina-brain axis, which has so far not been collectively examined. We propose that TIMP-3 activities could extend beyond its hitherto supposed functions to cause age-related changes and disease in these organs.
Competing Interests: Funding: This work was funded by awards to J.A.R. from Retina UK (GR590), the National Eye Research Centre (SAC 020) and the Macular Society UK, and to JMD from the Alzheimer’s Research UK (ARUK) South Coast Network. We are also grateful to the Gift of Sight Appeal for their support.
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معلومات مُعتمدة: GR590 International Retina UK; SAC 020 International National Eye Research Centre; PhD Studentship International Macular Society UK; Pump-prime award International Alzheimer's Research UK (ARUK) South Coast Network
فهرسة مساهمة: Keywords: AMD; Alzheimer’s disease; ECM; TIMP-3; dementia; retina; sorsby
المشرفين على المادة: 0 (Tissue Inhibitor of Metalloproteinase-3)
تواريخ الأحداث: Date Created: 20191228 Date Completed: 20200916 Latest Revision: 20200916
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7017234
DOI: 10.3390/cells9010039
PMID: 31877820
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells9010039