Abstract
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.
| Original language | English |
|---|---|
| Article number | 13818 |
| Pages (from-to) | 7-18 |
| Number of pages | 12 |
| Journal | Journal of the Neurological Sciences |
| Volume | 356 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Sep 15 2015 |
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Keywords
- Charcot-Marie-Tooth disease type 2A
- Clinical and genetic features
- Mitochondrial network
- Mitofusin 2
- Neurodegeneration
- Pathogenetic mechanisms
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
MFN2-related neuropathies : Clinical features, molecular pathogenesis and therapeutic perspectives. / Stuppia, Giulia; Rizzo, Federica; Riboldi, Giulietta; Del Bo, Roberto; Nizzardo, Monica; Simone, Chiara; Comi, Giacomo P.; Bresolin, Nereo; Corti, Stefania.
In: Journal of the Neurological Sciences, Vol. 356, No. 1-2, 13818, 15.09.2015, p. 7-18.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MFN2-related neuropathies
T2 - Clinical features, molecular pathogenesis and therapeutic perspectives
AU - Stuppia, Giulia
AU - Rizzo, Federica
AU - Riboldi, Giulietta
AU - Del Bo, Roberto
AU - Nizzardo, Monica
AU - Simone, Chiara
AU - Comi, Giacomo P.
AU - Bresolin, Nereo
AU - Corti, Stefania
PY - 2015/9/15
Y1 - 2015/9/15
N2 - 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.
AB - 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.
KW - Charcot-Marie-Tooth disease type 2A
KW - Clinical and genetic features
KW - Mitochondrial network
KW - Mitofusin 2
KW - Neurodegeneration
KW - Pathogenetic mechanisms
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UR - http://www.scopus.com/inward/citedby.url?scp=84939262128&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2015.05.033
DO - 10.1016/j.jns.2015.05.033
M3 - Article
C2 - 26143526
AN - SCOPUS:84939262128
VL - 356
SP - 7
EP - 18
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
M1 - 13818
ER -