{"id":2449,"date":"2013-09-06T00:00:00","date_gmt":"2013-09-06T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/"},"modified":"2013-09-06T00:00:00","modified_gmt":"2013-09-06T07:00:00","slug":"salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/","title":{"rendered":"Salk scientists and colleagues discover important mechanism underlying Alzheimer’s disease"},"content":{"rendered":"

LA JOLLA, CA\u2014Alzheimer’s disease<\/a> affects more than 26 million people worldwide. It is predicted to skyrocket as boomers age\u2014nearly 106 million people are projected to have the disease by 2050. Fortunately, scientists are making progress towards therapies. A collaboration among several research entities, including the Salk Institute and the Sanford-Burnham Medical Research Institute, has defined a key mechanism behind the disease’s progress, giving hope that a newly modified Alzheimer’s drug will be effective.<\/p>\n

\nIn a previous study in 2009, Stephen F. Heinemann<\/a>, a professor in Salk’s \u5206\u5b50\u795e\u7ecf\u751f\u7269\u5b66\u5b9e\u9a8c\u5ba4<\/a>, found that a nicotinic receptor called Alpha7 may help trigger Alzheimer’s disease. “Previous studies exposed a possible interaction between Alpha-7 nicotinic receptors (\u03b17Rs) with amyloid beta, the toxic protein found in the disease’s hallmark plaques,” says Gustavo Dziewczapolski, a staff researcher in Heinemann’s lab. “We showed for the first time, in vivo, that the binding of this two proteins, \t\u03b17Rs and amyloid beta, provoke detrimental effects in mice similar to the symptoms observed in Alzheimer’s disease .” <\/p>\n

\nTheir experiments, published in The Journal of Neuroscience<\/em>, with Dziewczapolski as first author, consisted in testing Alzheimer’s disease-induced mice with and without the gene for \t\u03b17Rs. They found that while both types of mice developed plaques, only the ones with \t\u03b17Rs showed the impairments associated with Alzheimer’s. <\/p>\n

\nBut that still left a key question: Why<\/em> was the pairing deleterious? <\/p>\n

\nIn a recent paper in the Proceedings of the National Academy of Sciences<\/a><\/em>, Heinemann and Dziewczapolski here at Salk with Juan Pi\u00f1a-Crespo, Sara Sanz-Blasco, Stuart A. Lipton of the Sanford-Burnham Medical Research Institute and their collaborators announced they had found the answer in unexpected interactions among neurons and other brain cells. <\/p>\n

\nNeurons communicate by sending electrical and chemical signals to each other across gaps called synapses. The biochemical mix at synapses resembles a major airport on a holiday weekend\u2014it’s crowded, complicated and exquisitely sensitive to increases and decreases in traffic. One of these signaling chemicals is glutamate, an excitatory neurotransmitter, which is essential for learning and storing memories. In the right balance, glutamate is part of the normal functioning of neuronal synapses. But neurons are not the only cells in the brain capable of releasing glutamate. Astrocytes, once thought to be merely cellular glue between neurons, also release this neurotransmitter. <\/p>\n

\nIn this new understanding of Alzheimer’s disease, there is a cellular signaling cascade, in which amyloid beta stimulates the alpha 7 nicotine receptors, which trigger astrocytes to release additional glutamate into the synapse, overwhelming it with excitatory (“go”) signals. <\/p>\n

\nThis release in turn activates another set of receptors outside of the synapse, called extrasynaptic-N-methyl-D-aspartate receptors (eNMDARs) that depress synaptic activity. Unfortunately, the eNMDARs seem to overly depress synaptic function, leading to the memory loss and confusion associated with Alzheimer’s.<\/p>\n

\nNow that the team has finally determined the steps in this destructive pathway, the good news is that a drug developed by the Lipton’s Laboratory called NitroMemantine, a modification of the earlier Alzheimer’s medication, Memantine, may block the entry of eNMDARs into the cascade.<\/p>\n

\n“Thanks to the joint effort of our colleagues and collaborators, we seem to finally have a clear mechanistic link between a key target of the amyloid beta in the brain, the Alpha7 nicotinic receptors, triggering downstream harmful effects associated with the initiation and progression of Alzheimer’s disease,” says Dziewczapolski. “This is a clear demonstration of the value of basic biomedical research. Drug development cannot proceed without knowing the details of interactions at the molecular and cellular level. Our research revealed two potential targets, \t\u03b17Rs and eNMDARs, for future disease-modifying therapeutics, which Dr. Heinemann and I both hope will translate in a better treatment for Alzheimer’s patients.” <\/p>\n

\nOther researchers on the study were Maria Talantova, Xiaofei Zhang, Peng Xia, Mohd Waseem Akhtar, Shu-ichi Okamoto, Tomohiro Nakamura, Gang Cao, Alexander E. Pratt, Yeon-Joo Kang, Shichun Tu, Elena Molokanova, Gary Tong, Scott R. McKercher, James Parker, Emily A. Holland, Traci Fang-Newmeyer, Dongxian Zhang, Nobuki Nakanishi, H.-S. Vincent Chen and Rajesh Ambasudhan of the Sanford-Burnham Medical Research Institute; Samuel Andrew Hires of the Howard Hughes Medical Research Institute; Herman Wolosker and Hagit Sason of the Technion-Israel Institute of Technology in Israel; Yuqiang Wang of Jinan University in China and Panorama Research Institute in California; Loren H. Parsons, David G. Stouffer, Matthew W. Buczynski, Amanda Roberts, James P. Solomon, Evan T. Powers and Jeffery W. Kelly of the Scripps Research Institute; Sarah Michael and Eliezer Masliah of UCSD School of Medicine.<\/p>\n

\nThis work was supported by the National Institutes of Health<\/a>, Department of Defense<\/a>, National Institute of Neurological Disorders and Stroke<\/a>, American Heart Association<\/a> and the Ministry of Education and Science of Spain.<\/p>\n


\nAbout the Salk Institute for Biological Studies:<\/strong><\/p>\n

The Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.\n<\/p>\n

\nFaculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[],"disease-research":[127,146,124],"class_list":["post-2449","disclosure","type-disclosure","status-publish","hentry","disease-research-alzheimers-disease","disease-research-aging-and-regenerative-medicine","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"\nSalk scientists and colleagues discover important mechanism underlying Alzheimer's disease - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salk scientists and colleagues discover important mechanism underlying Alzheimer's disease - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA, CA\u2014Alzheimer’s disease affects more than 26 million people worldwide. It is predicted to skyrocket as boomers age\u2014nearly 106 million people are projected to have the disease by 2050. Fortunately, scientists are making progress towards therapies. A collaboration among several research entities, including the Salk Institute and the Sanford-Burnham Medical Research Institute, has defined a key mechanism behind the disease’s progress, giving hope that a newly modified Alzheimer’s drug will be effective.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/zh\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"628\" \/>\n\t<meta property=\"og:image:height\" content=\"329\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\\\/\",\"name\":\"Salk scientists and colleagues discover important mechanism underlying Alzheimer's disease - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"datePublished\":\"2013-09-06T07:00:00+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\\\/#breadcrumb\"},\"inLanguage\":\"zh-CN\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Salk scientists and colleagues discover important mechanism underlying Alzheimer’s disease\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"zh-CN\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Salk scientists and colleagues discover important mechanism underlying Alzheimer's disease - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/zh\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/","og_locale":"zh_CN","og_type":"article","og_title":"Salk scientists and colleagues discover important mechanism underlying Alzheimer's disease - Salk Institute for Biological Studies","og_description":"LA JOLLA, CA\u2014Alzheimer’s disease affects more than 26 million people worldwide. It is predicted to skyrocket as boomers age\u2014nearly 106 million people are projected to have the disease by 2050. Fortunately, scientists are making progress towards therapies. A collaboration among several research entities, including the Salk Institute and the Sanford-Burnham Medical Research Institute, has defined a key mechanism behind the disease’s progress, giving hope that a newly modified Alzheimer’s drug will be effective.","og_url":"https:\/\/www.salk.edu\/zh\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/","og_site_name":"Salk Institute for Biological Studies","og_image":[{"width":628,"height":329,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"4 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/","url":"https:\/\/www.salk.edu\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/","name":"Salk scientists and colleagues discover important mechanism underlying Alzheimer's disease - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"datePublished":"2013-09-06T07:00:00+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/#breadcrumb"},"inLanguage":"zh-CN","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/salk-scientists-and-colleagues-discover-important-mechanism-underlying-alzheimers-disease\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Salk scientists and colleagues discover important mechanism underlying Alzheimer’s disease"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"zh-CN"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"paper_url":"http:\/\/www.pnas.org\/content\/early\/2013\/06\/13\/1306832110","journal_title":"PNAS","paper_author_list":"Gustavo Dziewczapolski and Stephen F. Heinemann of the Salk Institute; Stuart A. Lipton, Sara Sanz-Blasco, Maria Talantova, Xiaofei Zhang, Peng Xia, Mohd Waseem Akhtar, Shu-ichi Okamoto, Tomohiro Nakamura, Gang Cao, Alexander E. Pratt, Yeon-Joo Kang, Shichun Tu, Elena Molokanova, Gary Tong, Scott R. McKercher, James Parker, Emily A. Holland, Traci Fang-Newmeyer, Dongxian Zhang, Nobuki Nakanishi, H.-S. Vincent Chen, Rajesh Ambasudhan and Juan C. Piña-Crespo of the Sanford-Burnham Medical Research Institute; Samuel Andrew Hires of the Howard Hughes Medical Research Institute; Herman Wolosker and Hagit Sason of the Technion-Israel Institute of Technology in Israel; Yuqiang Wang of Jinan University in China and Panorama Research Institute in California; Loren H. Parsons, David G. Stouffer, Matthew W. Buczynski, Amanda Roberts, James P. Solomon, Evan T. Powers and Jeffery W. Kelly of the Scripps Research Institute; Sarah Michael and Eliezer Masliah of UCSD School of Medicine.","paper_title":"AΒ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss","subhead":"Details of destructive neuronal pathway should help improve drug therapies","home_photo":"632.jpg","listing_photo":"","line_2":"Details of destructive neuronal pathway should help improve drug therapies","line_1":"Salk scientists and colleagues discover important mechanism underlying Alzheimer's disease"},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/2449","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":0,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/2449\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media?parent=2449"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/faculty?post=2449"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disease-research?post=2449"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}