{"title":"Resolving the Molecular Steps in Clostridial Neurotoxin Light Chain Translocation.","authors":"Madison Zuverink, Joseph T Barbieri","doi":"10.33696/Neurol.1.020","DOIUrl":"https://doi.org/10.33696/Neurol.1.020","url":null,"abstract":"<p><p>The clostridial neurotoxins (CNTs), botulinum toxin and tetanus toxin, are the most toxic proteins for humans. Neurotoxicity is based upon the specificity of the CNTs for neural host receptors and substrates. CNTs are organized into three domains, a Light Chain (LC) that is a metalloprotease and a Heavy Chain (HC) that has two domains, an N-terminal LC translocation domain (HCN) and a C-terminal receptor binding domain (HCC). While catalysis and receptor binding functions of the CNTs have been developed, our understanding of LC translocation is limited. This is due to the intrinsic complexity of the translocation process and limited tools to assess the step-by-step events in LC translocation. Recently, we developed a novel, cell-based TT-reporter to measure LC translocation as the translocation of a β-lactamase reporter across a vesicle membrane in neurons. Using this approach, we identified a role for a <i>cis</i>-Loop, located within the HCN, in LC translocation. In this commentary, we describe our current understanding of how CNTs mediate LC translocation and place the role of the <i>cis</i>-Loop in the LC translocation process relative to other independent functions that have been implicated in LC translocation. Understanding the basis for LC translocation will enhance the use of CNTs in vaccine development and as human therapies.</p>","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"1 4","pages":"123-134"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25392325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brinda Desai Bradaric, Alana E Kirby, T Celeste Napier
{"title":"Integrating Neurology and Psychiatry throughout Educational Curricula for Healthcare Professionals.","authors":"Brinda Desai Bradaric, Alana E Kirby, T Celeste Napier","doi":"10.33696/neurol.1.026","DOIUrl":"https://doi.org/10.33696/neurol.1.026","url":null,"abstract":"We recently reviewed the scientific literature linking dopamine agonist pharmacotherapy for neurological disorders to the development of impulsive and compulsive spectrum disorders (ICSDs) [1]. This link was not clinically recognized until thousands of treated patients suffered from devastating emotional, financial and social difficulties associated with the cooccurring addictions. Here, we expand on this scientific overview to comment on how the clinical scenario emerged, and educational solutions to avoid similar consequences in the future. In brief, we hold that bridging the brain-centric disciplines (e.g., neurology and psychiatry) within medical education curricula and training is key. Teaching of these disciplines to future health professionals needs to emphasize integrated learning and practice to improve patient care.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"1 4","pages":"168-172"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38812018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}