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

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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 . https://doi.org/10.1080/15548627.2017.1388475

Title: Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B
Author: Colecchia, D; Stasi, M; Leonardi, M; Manganelli, F; Nolano, M; Veneziani, BM; Santoro, L; Eskelinen, Eeva-Liisa; Chiariello, M; Bucci, Cecilia
Other contributor: University of Helsinki, Biosciences


Date: 2018
Language: eng
Number of pages: 12
Belongs to series: Autophagy
ISSN: 1554-8627
DOI: https://doi.org/10.1080/15548627.2017.1388475
URI: http://hdl.handle.net/10138/238488
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.
Subject: 1182 Biochemistry, cell and molecular biology
autophagy
Charcot-Marie-Tooth disease
endocytosis peripheral neuropathy
RAB7
RAB7A
SPINAL-CORD-INJURY
RAB7 MUTATION
DISEASE
PROTEINS
CELLS
DEGENERATION
MATURATION
TRAFFICKING
ACTIVATION
VIMENTIN
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