{"id":106,"date":"2019-10-14T03:09:40","date_gmt":"2019-10-14T07:09:40","guid":{"rendered":"http:\/\/www.creativebiomart.org\/alzheimacy\/?page_id=106"},"modified":"2019-10-15T02:19:34","modified_gmt":"2019-10-15T06:19:34","slug":"tau-pathology-as-drug-targets","status":"publish","type":"page","link":"https:\/\/www.creativebiomart.net\/alzheimacy\/target\/tau-pathology-as-drug-targets\/","title":{"rendered":"Tau Pathology as Drug Targets"},"content":{"rendered":"<p>Neurofibrillary tangles (NFTs) are one of the primary neuropathological hallmarks of Alzheimer\u2019s disease (AD). NFTs are intracellular aggregates composed of the hyperphosphorylated tau protein. Physiologically, tau is a\u00a0natively unfolded, highly soluble microtubule-associated protein (MAP) that is found primarily in the central nervous system, specifically in the axons of mature neurons, and is involved in regulating the microtubule stability and intracellular trafficking.\u00a0The tau protein can undergo various forms of post-translational modifications, and the most extensively studied of which is phosphorylation. In AD, tau becomes hyperphosphorylated, and hyperphosphorylation of tau causes it to transform into paired helical filaments (PHFs) and NFTs. Pathological tau can cause microtubule disorders leading to neuronal degeneration.<\/p>\n<p><strong>Strategies Targeting<\/strong>\u00a0<strong>Tau Pathology <\/strong><\/p>\n<p>Each stage of tau pathology development, from the gene expression and splicing to post-translational modifications, aggregation, and impairments in clearance, offers potential opportunities for intervention.<\/p>\n<p class=\"ServiceShowPic\"><img decoding=\"async\" src=\"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-content\/themes\/alzheimacy\/images\/Tau-Pathology-as-Drug-Targets-1.jpg\" width=\"650\" \/><br \/>\nFigure 1.\u00a0Tau-related therapeutic targets and therapeutics.\u00a0(Wang Y, Mandelkow E. Tau in physiology and pathology. <em>Nature Reviews Neuroscience<\/em>. 2016, 17(1): 22.)<\/p>\n<ul>\n<li><a href=\"\/alzheimacy\/target\/tau-pathology-as-drug-targets\/targeting-tau-expression\/\">Targeting Tau Expression<\/a><\/li>\n<li><a href=\"\/alzheimacy\/target\/tau-pathology-as-drug-targets\/targeting-tau-aggregation\/\">Targeting Tau Aggregation and Clearance<\/a><\/li>\n<li><a href=\"\/alzheimacy\/target\/tau-pathology-as-drug-targets\/tau-immunotherapies\/\">Tau Immunotherapies<\/a><\/li>\n<\/ul>\n<p><strong>Current Status of Tau-targeting Therapeutics for AD <\/strong><\/p>\n<p>The development of therapeutics for AD has focused mainly on\u00a0<a href=\"\/alzheimacy\/target\/abeta-amyloid-pathway-as-drug-targets\/\">amyloid \u03b2 (A\u03b2)<\/a>, but most drug development based on the A\u03b2 cascade hypothesis ends in clinical failure, suggesting that A\u03b2 may not be the best therapeutic target. Besides, given that tau pathology correlates better with neuron loss and cognitive impairment than do A\u03b2 lesions, tau-targeting strategies have received more attention in recent years.<\/p>\n<p>Early potential anti-tau therapeutics were\u00a0based primarily on inhibiting pathological tau phosphorylation or aggregation, or on stabilizing microtubules, but most of these approaches have been discontinued due to adverse reactions or lack of efficacy. Currently, most of the tau-targeting therapeutics in clinical trials are immunotherapies. Moreover, continuing basic research on the underlying causes of AD and the mechanism of tau pathology is crucial to identify novel targets.<\/p>\n<p>If you are paying attention to\u00a0tau-targeting therapeutics and are looking for further research advances, Alzheimacy can meet your needs for <a href=\"\/alzheimacy\/solutions\/basic-research\/\">basic<\/a>\u00a0and <a href=\"\/alzheimacy\/solutions\/preclinical-development\/\">preclinical research<\/a>. Please feel free to <a href=\"\/alzheimacy\/contact-us\/\">contact us<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Neurofibrillary tangles (NFTs) are one of the primary neuropathological hallmarks of Alzheimer\u2019s disease (AD). NFTs are intracellular aggregates composed of the hyperphosphorylated tau protein. Physiologically, tau is a\u00a0natively unfolded, highly soluble microtubule-associated protein (MAP) that is found primarily in the central nervous system, specifically in the axons of mature neurons, and is involved in regulating [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":9,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/pages\/106"}],"collection":[{"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/comments?post=106"}],"version-history":[{"count":5,"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/pages\/106\/revisions"}],"predecessor-version":[{"id":152,"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/pages\/106\/revisions\/152"}],"up":[{"embeddable":true,"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/pages\/9"}],"wp:attachment":[{"href":"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-json\/wp\/v2\/media?parent=106"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}