title: MFN2-related neuropathies: Clinical features, molecular pathogenesis and therapeutic perspectives.
abstract: Mitofusin 2 (MFN2) is a GTPase dynamin-like protein of the outer mitochondrial membrane, encoded in the nuclear genome by the MFN2 gene located on the short (p) arm of chromosome 1. MFN2 protein is involved in several intracellular pathways, but is mainly involved in a network that has an essential role in several mitochondrial functions, including fusion, axonal transport, interorganellar communication and mitophagy. Mutations in the gene encoding MFN2 are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a wide clinical phenotype that involves the central and peripheral nervous system. Here, we present the clinical, genetic and neuropathological features of human diseases associated with MFN2 mutations. We also report proposed pathogenic mechanisms through which MFN2 mutations likely contribute to the development of neurodegeneration. MFN2-related disorders may occur more frequently than previously considered, and they may represent a paradigm for the study of the defective mitochondrial dynamics that seem to play a significant role in the molecular and cellular pathogenesis of common neurodegenerative diseases; thus they may also lead to the identification of related therapeutic targets.
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Stuppia
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzo
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Riboldi
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy. Electronic address: stefania.corti@unimi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
mesh_terms: D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: Charcot–Marie–Tooth disease type 2A; Clinical and genetic features; Mitochondrial network; Mitofusin 2; Neurodegeneration; Pathogenetic mechanisms