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The inhibition or reversal of tau aggregation is a potential therapeutic strategy that is currently undergoing clinical trials. The image shows pathological fibers assembled from tau protein, which are the main components of the neurofibrillary tangles of Alzheimer's disease.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/gif\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/mcontent.gif\">\n                        <jats:alt-text>magnified image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>\n                  <jats:p>A variety of human diseases are suspected to be directly linked to protein misfolding. Highly organized protein aggregates, called amyloid fibrils, and aggregation intermediates are observed; these are considered to be mediators of cellular toxicity and thus attract a great deal of attention from investigators. Neurodegenerative pathologies such as Alzheimer's disease account for a major part of these protein misfolding diseases. The last decade has witnessed a renaissance of interest in inhibitors of tau aggregation as potential disease\u2010modifying drugs for Alzheimer's disease and other \u201ctauopathies\u201d. The recent report of a phase\u2005II clinical trial with the tau aggregation inhibitor MTC could hold promise for the validation of the concept. This Review summarizes the available data concerning small\u2010molecule inhibitors of tau aggregation from a medicinal chemistry point of view.<\/jats:p>","DOI":"10.1002\/anie.200802621","type":"journal-article","created":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T10:09:57Z","timestamp":1233569397000},"page":"1740-1752","source":"Crossref","is-referenced-by-count":253,"title":["Development of Tau Aggregation Inhibitors for Alzheimer's Disease"],"prefix":"10.1002","volume":"48","author":[{"given":"Bruno","family":"Bulic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Pickhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva\u2010Maria","family":"Mandelkow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Waldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckhard","family":"Mandelkow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0502-323"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867023370167"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21051"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2003.09.007"},{"key":"e_1_2_7_5_2","unstructured":"L. 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