A group led by Domenico Pratico, professor of pharmacology and microbiology and immunology at Temple, discovered the presence of the protein, called 12\/15-Lipoxygenase<\/strong>, in the brain three years ago.<\/p>\n \u201cWe found this protein to be very active in the brains of people who have Alzheimer\u2019s disease,\u201d said Pratico. \u201cBut three years ago, we didn\u2019t know the role it played in the development of the disease.\u201d<\/p>\n Following two years of study, the Temple researchers have found that the protein is at the top of a pathway and controls a biochemical chain reaction that begins the development of Alzheimer\u2019s. They have published their findings, \u201cTranscriptional Regulation of \u00dfsecretase-1 by 12\/15 Lipoxygenase Results in Enhanced Amyloidogenesis and Cognitive Impairments,\u201d in the journal Annals of Neurology.<\/em><\/p>\n Pratico said that their research has shown that 12\/15-Lipoxygenase controls Beta secretase (BACE-1), an enzyme that is key to the development of amyloid plaques in Alzheimer\u2019s patients.<\/p>\n \u201cFor reasons we don\u2019t yet know, in some people, 12\/15-Lipoxygenase starts to work too much,\u201d he said. \u201cBy working too much, it sends the wrong message to the Beta secretase, which in turn starts to produce more amyloid beta. This initially results in cognitive impairment, memory impairment and, later, an increase of amyloid plaque.\u201d<\/p>\n BACE-1 has long been a biological target for researchers seeking to create a drug against Alzheimer\u2019s disease, said Pratico. But because little has been known about how it functions, they have been unsuccessful developing a molecule that could reach the brain and block it.<\/p>\n \u201cWe now know much better how Beta secretase works because we have found that the 12\/15-Lipoxygenase protein is a controller of BACE functions,\u201d he said. \u201cYou don\u2019t need to target the Beta secretase directly because the 12\/15-Lipoxygenase is really the system in the brain that tells BACE to work more or work less.\u201d<\/p>\n Pratico said that they have validated 12\/15-Lipoxygenase as a target for a potential Alzheimer drug or therapy.<\/p>\n \u201cBy modulating BACE levels and activity through controlling the 12\/15-Lipoxygenase, we can potentially improve the cognitive part of the phenotype of the disease, and prevent the accumulation of amyloid beta inside the neurons, which will eventually translate into less of those plaques,\u201d he said. \u201cThis is a totally new mechanism for controlling BACE.\u201d<\/p>\n Pratico said his group has looked at an experimental compound that blocks 12\/15-Lipoxygenase function as a potential therapy to inhibit BACE function in the brain. In their lab, using animal models, they saw the drug\u2019s ability to restore some cognitive function, as well as improve learning and memory ability.<\/strong><\/p>\n \u201cThere is an opportunity here to study this molecule and develop an even stronger molecule to target 12\/15-Lipoxygenase function in the brain,\u201d he said.<\/p>\n The study was funded by the National Institutes of Health and the Alzheimer\u2019s Association.<\/p><\/blockquote>\n","protected":false},"excerpt":{"rendered":" From the Temple University press release: A protein recently discovered in the brain could play a key role in regulating the creation of amyloid beta, the major component of plaques… Read more »<\/a><\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[4,6],"tags":[16,195,42,18,194,49],"_links":{"self":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/1014"}],"collection":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/comments?post=1014"}],"version-history":[{"count":1,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/1014\/revisions"}],"predecessor-version":[{"id":1015,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/1014\/revisions\/1015"}],"wp:attachment":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/media?parent=1014"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/categories?post=1014"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/tags?post=1014"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"\"](\"http:\/\/therapytoronto.ca\/images\/blogpics\/Brain.jpg\" "\\"brain\\"")
A protein recently discovered in the brain could play a key role in regulating the creation of amyloid beta, the major component of plaques implicated in the development of Alzheimer\u2019s disease<\/strong>, according to researchers at Temple University\u2019s School of Medicine.<\/p>\n