Cellular and Molecular Neurobiology<\/p>\n
Author:<\/strong> Fiamma Ayelen Buratti | Email:<\/strong> fburatti@cei-mplbior.unr.edu.ar<\/p>\n Fiamma Ayelen Buratti 1\u00b0<\/sup>, Markus Zweckstetter 2\u00b0<\/sup>, Claudio Oscar Fern\u00e1ndez 1\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. Parkinson’s disease can manifest either as a sporadic form, which is common or as an inherited autosomal dominant trait resulting from missense mutations. Nine potentially pathogenic variants of \u03b1-synuclein (\u03b1Syn) associated with familial PD have been identified to date. This includes the well-studied A30P, E46K and A53T variants, as well as A30G, H50Q, G51D, A53E, and A53V. Recently, the novel \u0251-synuclein variant V15A was identified in two Caucasian and two Japanese families with Parkinson\u2019s disease. Using a combination of NMR spectroscopy, membrane binding assays, and aggregation assays we show that the V15A mutation does not strongly perturb the conformational ensemble of monomeric \u0251-synuclein in solution, but weakens its affinity for membranes. Attenuated membrane binding raises the concentration of the aggregation-prone disordered \u0251-synuclein in solution, allowing only the V15A variant but not wild-type \u0251-synuclein to form amyloid fibrils in the presence of liposomes. These findings, together with earlier research on other missense mutations of \u0251-synuclein, suggest that maintaining a balance between membrane-bound and free aggregation-competent \u0251-synuclein is critical in \u0251-synucleinopathies.<\/p>\n","protected":false},"excerpt":{"rendered":" Author: Buratti Fiamma Ayelen | email: fburatti@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":[34],"tags":[18],"class_list":["post-1883","post","type-post","status-publish","format-standard","hentry","category-session-2","tag-cellular-and-molecular-neurobiology"],"_links":{"self":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1883","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=1883"}],"version-history":[{"count":1,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1883\/revisions"}],"predecessor-version":[{"id":2030,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1883\/revisions\/2030"}],"wp:attachment":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/media?parent=1883"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/categories?post=1883"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/tags?post=1883"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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\n2\u00b0 German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 G\u00f6ttingen, Germany.<\/p>\n