Cellular and Molecular Neurobiology<\/p>\n
Author:<\/strong> Nicola Martina B\u00f6ffinger | Email:<\/strong> nboeffinger@cei-mplbior.unr.edu.ar<\/p>\n Nicola B\u00f6ffinger 1\u00b0<\/sup>, Stefan Eimer 3\u00b0<\/sup>, Claudio O. Fern\u00e1ndez 1\u00b0<\/sup>, Christian Griesinger 2\u00b0<\/sup><\/p>\n 1\u00b0 Max Planck Laboratory for Structural Biology, Chemistry, and Molecular Biophysics of Rosario (MPLbioR, UNR-MPINAT), Partner Laboratory of the Max Planck Institute for Multidisciplinary Sciences (MPINAT, MPG). Centro de Estudios Interdisciplinarios, Universidad Nacional de Rosario, Rosario, Argentina. Altered protein aggregation and accumulation is associated with different neurodegenerative diseases such as Creutzfeldt-Jakob\u2019s, Alzheimer or Parkinson disease (PD). The latter is classified as synucleinopathy, which is characterized by the abnormal aggregation and accumulation of \u03b1-synuclein (\u03b1Syn), forming oligomers and fibrils. Less is known about the toxic species of \u03b1Syn aggregates. However, with regards to its aggregation it has been discovered that next to the central non-amyloid \u03b2-component region (NAC) of \u03b1Syn further N-terminal regions are crucial. One of these regions expands over residues 36-42, whose elimination prevents protein aggregation. Y39 is located within this region and was found to be phosphorylated in advanced stages of PD. The mutation Y39E imitates this phosphorylation and allows to study its impact on protein aggregation and toxicity. Using biophysical methods such as NMR and circular dichroism amongst others we found that the Y39E \u03b1Syn variant has a different aggregation profile compared to the wild-type species. NMR studies revealed that that the structural features of Y39E \u03b1Syn, at a monomeric level, does not differ significantly from WT \u03b1Syn, thus changes in aggregation from the transition of monomers into oligomers and\/or fibrils are likely due the loss of function of Tyr at position 39 of the protein. Results focused on membrane binding and toxicity in cell and animal models for \u03b1Syn aggregation validate the measurements performed in vitro.<\/p>\n","protected":false},"excerpt":{"rendered":" Author: B\u00f6ffinger Nicola Martina | email: nboeffinger@cei-mplbior.unr.edu.ar | Cellular and Molecular Neurobiology<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[17],"tags":[18],"class_list":["post-1229","post","type-post","status-publish","format-standard","hentry","category-session-1","tag-cellular-and-molecular-neurobiology"],"_links":{"self":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1229","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/comments?post=1229"}],"version-history":[{"count":4,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1229\/revisions"}],"predecessor-version":[{"id":2421,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1229\/revisions\/2421"}],"wp:attachment":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/media?parent=1229"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/categories?post=1229"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/tags?post=1229"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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\n2\u00b0 Max Planck Institute for Multidisciplinary Sciences, Department of NMR-based Structural Biology, Am Fassberg 11, 37077 G\u00f6ttingen, Germany.
\n3\u00b0 Goethe University, Frankfurt, Germany<\/p>\n