{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T08:26:28Z","timestamp":1768033588325,"version":"3.49.0"},"reference-count":140,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL055374"],"award-info":[{"award-number":["HL055374"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NS079639"],"award-info":[{"award-number":["NS079639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NS007222"],"award-info":[{"award-number":["NS007222"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AG052934"],"award-info":[{"award-number":["AG052934"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Michigan Protein Folding Disease Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tissue plasminogen activator's (tPA) fibrinolytic function in the vasculature is well-established. This specific role for tPA in the vasculature, however, contrasts with its pleiotropic activities in the central nervous system. Numerous physiological and pathological functions have been attributed to tPA in the central nervous system, including neurite outgrowth and regeneration; synaptic and spine plasticity; neurovascular coupling; neurodegeneration; microglial activation; and blood\u2013brain barrier permeability. In addition, multiple substrates, both plasminogen-dependent and -independent, have been proposed to be responsible for tPA's action(s) in the central nervous system. This review aims to dissect a subset of these different functions and the different molecular mechanisms attributed to tPA in the context of learning and memory. We start from the original research that identified tPA as an immediate-early gene with a putative role in synaptic plasticity to what is currently known about tPA's role in a learning and memory disorder, Alzheimer's disease. We specifically focus on studies demonstrating tPA's involvement in the clearance of amyloid-\u03b2 and neurovascular coupling. In addition, given that tPA has been shown to regulate blood\u2013brain barrier permeability, which is perturbed in Alzheimer's disease, this review also discusses tPA-mediated vascular dysfunction and possible alternative mechanisms of action for tPA in Alzheimer's disease pathology.<\/jats:p>","DOI":"10.1055\/s-0041-1740265","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T23:47:29Z","timestamp":1640303249000},"page":"288-300","source":"Crossref","is-referenced-by-count":9,"title":["Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease"],"prefix":"10.1055","volume":"48","author":[{"given":"Tamara K.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, Michigan"},{"name":"Department of Molecular and Integrative Physiology, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon J.","family":"Moore","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, Michigan"},{"name":"Department of Molecular and Integrative Physiology, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey G.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, Michigan"},{"name":"Department of Molecular and Integrative Physiology, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan"},{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/361453a0","article-title":"Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation","volume":"361","author":"Z Qian","year":"1993","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1126\/science.270.5244.1992","article-title":"Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning","volume":"270","author":"N W 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