{"id":25783,"date":"2015-11-12T16:27:12","date_gmt":"2015-11-12T21:27:12","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/busm\/?p=25783"},"modified":"2015-11-12T16:27:12","modified_gmt":"2015-11-12T21:27:12","slug":"discovery-molecular-mechanism-at-root-of-familial-amyloidosis-and-other-diseases","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2015\/11\/12\/discovery-molecular-mechanism-at-root-of-familial-amyloidosis-and-other-diseases\/","title":{"rendered":"Discovery: Molecular Mechanism at Root of Familial Amyloidosis and Other Diseases"},"content":{"rendered":"

A team of local researchers has proposed a molecular mechanism that may be responsible for the development of life-threatening diseases called amyloidoses. The best known of such diseases is Alzheimer\u2019s disease (AD), but there are many others that are receiving increased scrutiny, in part because of mounting evidence linking them to atherosclerosis and aging.<\/p>\n

\"COMThe findings, which appear in the Journal of Molecular Biology, <\/em>may ultimately lead to the development of therapeutic targets for one of these diseases.<\/p>\n

A group of disorders, called amyloid diseases, occurs due to proteins that form abnormal clumps and deposit in different organs, causing damage to the brain (AD, Parkinson\u2019s disease), heart (cardiac amyloidosis), kidney, liver and other vital organs. One such protein called apolipoprotein A-1 (apoA-1) forms the scaffold of the so-called \u201cgood cholesterol,\u201d or high-density lipoprotein (HDL). Normally, apoA-1\/HDL removes excess cholesterol and other fats from the body and is protective against cardiovascular disease. However, when mutations or other errors occur within this protein, apoA-1 has the potential to aggregate and manifest as familial form of amyloidosis, which is a life-threatening incurable disease. ApoA-I can also deposit in arteries, thereby contributing to atherosclerosis. While the medical community has known for some time that abnormal proteins can cause disease due to exposed vulnerable \u201chot spots\u201d that clump together, there has been a lack of understanding about how a \u201cgood\u201d protein can become so \u201cbad,\u201d especially at a molecular level.<\/p>\n

Using cutting-edge technology to study the dynamic behavior and molecular shape of apoA-1 and its various mutant forms, researchers at Boston University School of Medicine (BUSM) and Northeastern University were surprised to discover that exposed \u201chot spots\u201d in apoA-I do not always cause amyloid disease. Some mutations led to decreased protection in other vulnerable parts, which helped the body to get rid of the protein before it clumps. These mutations in apoA-I did not cause amyloid disease in humans. The researchers suggest that this finding is not limited to apoA-I but possibly applies to other amyloid-forming proteins. Surprisingly, some mutations occurring at one end of the protein acted like \u201cmolecular remote-controls\u201d and changed the structure and activity of the other end.<\/p>\n

According to the researchers, solving the puzzle of the molecular changes that cause amyloid diseases has important implications for potential treatments. \u201cIf one could predict what makes any given protein to form amyloid, one could begin to design tools to decelerate or even block this pathogenic process before it starts,\u201d explained corresponding author Olga Gursky, PhD, professor of Physiology and Biophysics at BUSM.<\/p>\n

Funding for this study was provided by the National Institutes of Health grants GM067260 (to Olga Gursky, BUSM) and GM101135 (to John Engen, NEU), with additional support from Waters Corporation (John Engen). Dr. Xiaohu Mei was supported by the NIH grant HL116518 (to David Atkinson, BUSM).<\/p>\n","protected":false},"excerpt":{"rendered":"

Corresponding author Olga Gursky, PhD, professor of Physiology and Biophysics, explains this may ultimately lead to the development of therapeutic targets for one of these diseases<\/p>\n","protected":false},"author":903,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[91,90],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/25783"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/users\/903"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/comments?post=25783"}],"version-history":[{"count":3,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/25783\/revisions"}],"predecessor-version":[{"id":25793,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/25783\/revisions\/25793"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=25783"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=25783"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=25783"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}