{"id":18364,"date":"2015-09-17T14:08:24","date_gmt":"2015-09-17T18:08:24","guid":{"rendered":"http:\/\/therapytoronto.ca\/news\/?p=18364"},"modified":"2015-09-17T14:29:41","modified_gmt":"2015-09-17T18:29:41","slug":"alzheimers-disease-related-proteases-control-axonal-guidance-by-regulating-growth-cone-dynamics","status":"publish","type":"post","link":"https:\/\/therapytoronto.ca\/news\/2015\/09\/alzheimers-disease-related-proteases-control-axonal-guidance-by-regulating-growth-cone-dynamics\/","title":{"rendered":"Alzheimer&#8217;s-disease-related proteases control axonal guidance by regulating growth cone dynamics"},"content":{"rendered":"<p>From the VIB (Flanders Interuniversity Institute for Biotechnology) media release:<\/p>\n<blockquote>\n<p id=\"first\" class=\"lead\"><strong><a href=\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2013\/08\/schizophrenia-memory-loss-2.jpg\"><img loading=\"lazy\" class=\"alignright size-full wp-image-15339\" src=\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2013\/08\/schizophrenia-memory-loss-2.jpg\" alt=\"memory loss\" width=\"280\" height=\"275\" \/><\/a>BACE1 is the major drug target for Alzheimer&#8217;s disease<\/strong>, but we know surprisingly little about its normal function in the CNS.<\/p>\n<p class=\"lead\">Soraia Bar\u00e3o and Bart De Strooper (VIB\/KU Leuven) now show that <strong>this protease is critically involved in axonal guidance processes in thalamic and hippocampal neurons<\/strong>. An active membrane bound proteolytic CHL1 fragment is generated by BACE1 upon Sema3A binding. This fragment relays the Sema3A signal to the neuronal cytoskeleton. APH1B-y-secretase- mediated degradation of this fragment stops the Sema3A-induced collapse and sensitizes the growth cone for the next axonal guidance cue.<\/p>\n<div id=\"text\">\n<p>Soraia Bar\u00e3o (VIB\/KU Leuven): &#8220;We reveal a cycle of proteolytic activity underlying growth cone collapse and restoration used by axons to find their correct trajectory in the brain. <strong>Our data show that BACE1 and y-secretase inhibition have physiologically opposite effects in this process<\/strong>, suggesting that cautiously-designed combination therapies might attenuate some of the side effects associated with these drugs.&#8221;<\/p>\n<p>Bart De Strooper (VIB\/KU Leuven): &#8220;<strong>Based on this new knowledge of the functions of both proteases (BACE1 cleaves CHL1, inducing growth cone collapse.<\/strong> Subsequently, y-secretase activity stops the collapse and axonal growth resumes.), we think it wise to proceed the testing of inhibitors of these proteases in humans with caution.&#8221;<\/p>\n<\/div>\n<\/blockquote>\n<!-- AddThis Advanced Settings generic via filter on the_content --><!-- AddThis Share Buttons generic via filter on the_content -->","protected":false},"excerpt":{"rendered":"<p>From the VIB (Flanders Interuniversity Institute for Biotechnology) media release: BACE1 is the major drug target for Alzheimer&#8217;s disease, but we know surprisingly little about its normal function in the&#8230; <a class=\"read-more-link\" href=\"https:\/\/therapytoronto.ca\/news\/2015\/09\/alzheimers-disease-related-proteases-control-axonal-guidance-by-regulating-growth-cone-dynamics\/\">Read more &raquo;<\/a><!-- AddThis Advanced Settings generic via filter on get_the_excerpt --><!-- AddThis Share Buttons generic via filter on get_the_excerpt --><\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[321,358,4,6],"tags":[],"_links":{"self":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/18364"}],"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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/comments?post=18364"}],"version-history":[{"count":2,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/18364\/revisions"}],"predecessor-version":[{"id":18371,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/18364\/revisions\/18371"}],"wp:attachment":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/media?parent=18364"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/categories?post=18364"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/tags?post=18364"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}