Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B

Show simple item record Colecchia, D Stasi, M Leonardi, M Manganelli, F Nolano, M Veneziani, BM Santoro, L Eskelinen, Eeva-Liisa Chiariello, M Bucci, Cecilia 2018-08-16T07:28:01Z 2018-08-16T07:28:01Z 2018
dc.identifier.citation Colecchia , D , Stasi , M , Leonardi , M , Manganelli , F , Nolano , M , Veneziani , BM , Santoro , L , Eskelinen , E-L , Chiariello , M & Bucci , C 2018 , ' Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B ' , Autophagy , vol. 14 , no. 6 , pp. 930-941 .
dc.identifier.other PURE: 93307436
dc.identifier.other PURE UUID: c1d5af67-df7f-4d51-8b41-263687af5342
dc.identifier.other Scopus: 85045761121
dc.identifier.other WOS: 000441263100002
dc.identifier.other ORCID: /0000-0003-0006-7785/work/47604850
dc.description.abstract Charcot-Marie-Tooth type 2B (CMT2B) disease is a dominant axonal peripheral neuropathy caused by 5 mutations in the RAB7A gene, a ubiquitously expressed GTPase controlling late endocytic trafficking. In neurons, RAB7A also controls neuronal-specific processes such as NTF (neurotrophin) trafficking and signaling, neurite outgrowth and neuronal migration. Given the involvement of macroautophagy/autophagy in several neurodegenerative diseases and considering that RAB7A is fundamental for autophagosome maturation, we investigated whether CMT2B-causing mutants affect the ability of this gene to regulate autophagy. In HeLa cells, we observed a reduced localization of all CMT2B-causing RAB7A mutants on autophagic compartments. Furthermore, compared to expression of RAB7AWT, expression of these mutants caused a reduced autophagic flux, similar to what happens in cells expressing the dominant negative RAB7AT22N mutant. Consistently, both basal and starvation-induced autophagy were strongly inhibited in skin fibroblasts from a CMT2B patient carrying the RAB7AV162M mutation, suggesting that alteration of the autophagic flux could be responsible for neurodegeneration. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Autophagy
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 1182 Biochemistry, cell and molecular biology
dc.subject autophagy
dc.subject Charcot-Marie-Tooth disease
dc.subject endocytosis peripheral neuropathy
dc.subject RAB7
dc.subject RAB7A
dc.subject RAB7 MUTATION
dc.subject DISEASE
dc.subject PROTEINS
dc.subject CELLS
dc.subject MATURATION
dc.subject TRAFFICKING
dc.subject ACTIVATION
dc.subject VIMENTIN
dc.title Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B en
dc.type Article
dc.contributor.organization Biosciences
dc.contributor.organization Biochemistry and Biotechnology
dc.contributor.organization Autophagy
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1554-8627
dc.rights.accesslevel openAccess
dc.type.version publishedVersion
dc.relation.funder European Union
dc.relation.funder Acedemy of Finland

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