{"id":13339,"date":"2017-06-20T19:06:46","date_gmt":"2017-06-20T23:06:46","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/?p=13339"},"modified":"2026-01-07T15:14:46","modified_gmt":"2026-01-07T20:14:46","slug":"new-research-discoveries-prion-proteins-and-neuron-degeneration","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/2017\/06\/20\/new-research-discoveries-prion-proteins-and-neuron-degeneration\/","title":{"rendered":"New Research Discoveries: Prion proteins and neuron degeneration"},"content":{"rendered":"<p>A new paper in <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28527237\">eLife<\/a> from the <a href=\"https:\/\/www.bumc.bu.edu\/biochemcellbio\/profiles\/david-a-harris\/\">Harris lab<\/a> has uncovered a novel function for different domains of the prion protein. Bei Wu, an Instructor in the laboratory was lead author.<\/p>\n<p><img loading=\"lazy\" src=\"\/biochemcellbio\/files\/2017\/06\/Screen-Shot-2017-06-20-at-7.03.51-PM-341x300.png\" alt=\"\" width=\"341\" height=\"300\" class=\"alignright size-medium wp-image-13341\" srcset=\"https:\/\/www.bumc.bu.edu\/biochemcellbio\/files\/2017\/06\/Screen-Shot-2017-06-20-at-7.03.51-PM-341x300.png 341w, https:\/\/www.bumc.bu.edu\/biochemcellbio\/files\/2017\/06\/Screen-Shot-2017-06-20-at-7.03.51-PM.png 738w\" sizes=\"(max-width: 341px) 100vw, 341px\" \/><\/p>\n<p>Prion diseases, or transmissible spongiform encephalopathies, comprise a group of fatal neurodegenerative disorders in humans and animals for which there are no effective treatments or cures. These diseases are caused by refolding of the cellular prion protein (PrP<sup>C<\/sup>) into an infectious isoform (PrP<sup>Sc<\/sup>) that catalytically templates its abnormal conformation onto additional molecules of PrP<sup>C<\/sup>.A similar, prion-like process may play a role in other neurodegenerative disorders, such as Alzheimer\u2019s and Parkinson\u2019s diseases and tauopathies, which are due to protein misfolding and aggregation. Here, using a combination of electrophysiological, cellular, and biophysical techniques, we show that the flexible, N-terminal domain of PrP<sup>C<\/sup> functions as a powerful toxicity-transducing effector whose activity is tightly regulated <em>in cis<\/em> by the globular C-terminal domain. Ligands binding to the N-terminal domain abolish the spontaneous ionic currents associated with neurotoxic mutants of PrP, and the isolated N-terminal domain induces currents when expressed in the absence of the C-terminal domain. Anti-PrP antibodies targeting epitopes in the C-terminal domain induce currents, and cause degeneration of dendrites on murine hippocampal neurons, effects that entirely dependent on the effector function of the N-terminus. NMR experiments demonstrate intramolecular docking between N- and C-terminal domains of PrP<sup>C<\/sup>, revealing a novel auto-inhibitory mechanism that regulates the functional activity of PrP<sup>C<\/sup>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A new paper in eLife from the Harris lab has uncovered a novel function for different domains of the prion [&hellip;]<\/p>\n","protected":false},"author":1191,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[104,4658,100],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/posts\/13339"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/users\/1191"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/comments?post=13339"}],"version-history":[{"count":6,"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/posts\/13339\/revisions"}],"predecessor-version":[{"id":15581,"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/posts\/13339\/revisions\/15581"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/media?parent=13339"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/categories?post=13339"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/biochemcellbio\/wp-json\/wp\/v2\/tags?post=13339"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}