{"id":118436,"date":"2023-12-07T12:34:47","date_gmt":"2023-12-07T17:34:47","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/camed\/?p=118436"},"modified":"2023-12-07T12:34:47","modified_gmt":"2023-12-07T17:34:47","slug":"researchers-determine-structural-basis-for-apoe-a%ce%b2-interactions","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2023\/12\/07\/researchers-determine-structural-basis-for-apoe-a%ce%b2-interactions\/","title":{"rendered":"Researchers Determine Structural Basis for ApoE-A\u03b2 Interactions"},"content":{"rendered":"

Alzheimer\u2019s disease (AD) is a debilitating incurable disease that affects millions of patients worldwide. Deposits of amyloid beta (A\u03b2) amyloid in the brain is key to AD pathology at early stages. Apolipoprotein E<\/span> (apoE) interacts with A\u03b2 and can influence this pathologic process. Although apoE-A\u03b2 interactions have been extensively studied and have been proposed as a therapeutic target in AD, results of prior studies are confusing. Some report that apoE promotes A\u03b2 amyloid formation while others report that apoE blocks this pathological process.<\/p>\n

A new biophysical study<\/a> from researchers at the school explains why apoE and other apolipoproteins co-deposit with amyloids and provides a structural basis for understanding how apolipoproteins modulate amyloid growth and proliferation in the body.<\/p>\n

\u201cOur analysis of four different amyloid fibrils shows that apoE-amyloid interactions depend on the exact amyloid structure, termed polymorph. Amyloid polymorphs are disease- and tissue-specific and can be different in different experiments, which explains discrepancies among prior studies. Understanding such disease-specific factors is essential for harnessing apoE-A\u03b2 interactions for therapeutic targeting,\u201d explains first author Emily Lewkowicz, a PhD candidate in biophysics at the school.<\/p>\n

The researchers used four different structures of A\u03b2 fibrils from brains of patients with Alzheimer\u2019s and other neurodegenerative diseases. To build models of apoE in complexes with different fibrils, they performed protein docking (the prediction of the structure of the complex, based on the structures of the individual proteins) using computer modeling, followed by molecular dynamics simulations to test the stability of the complex.<\/span> The computational results, taken together with prior experimental data, revealed the driving forces and the molecular mechanisms for apolipoprotein binding to amyloid fibrils.<\/p>\n

\"photoAccording to the researchers, apolipoproteins such as apoE are \u201camyloid signature proteins\u201d that are found in amyloid deposits and probably influence their formation. \u201cOur work shows how these proteins can interact directly with various amyloids and thereby promote or block their growth and proliferation by binding alongside fibrils or at their ends\u201d adds corresponding author Olga Gursky<\/a>, PhD, professor of pharmacology, physiology & biophysics at the school.<\/p>\n

Besides A\u03b2, nearly 40 other proteins form pathologic amyloids in various human diseases, including Parkinson\u2019s disease, chronic traumatic encephalopathy, light chain amyloidosis, and many other life-threatening disorders. Apolipoproteins such as apoE are found in all these amyloid deposits. This work shows how these proteins can interact directly with amyloids and thereby influence their physical and biological properties.<\/p>\n

Also involved in this study were Michael J. Rynkiewicz<\/a>, PhD, instructor of pharmacology, physiology & biophysics at the school, and Mari N. Nakamura, an undergraduate summer student from Middlebury College.<\/p>\n

These findings appear<\/a> online in Cellular and Molecular Life Sciences Journal.<\/p>\n","protected":false},"excerpt":{"rendered":"

The biophysical study explains why apoE and other apolipoproteins co-deposit with amyloids and provides a structural basis for understanding how apolipoproteins modulate amyloid growth and proliferation in the body.<\/p>\n","protected":false},"author":903,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[90],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/118436"}],"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=118436"}],"version-history":[{"count":3,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/118436\/revisions"}],"predecessor-version":[{"id":118440,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/118436\/revisions\/118440"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=118436"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=118436"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=118436"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}