title: [Pathomechanisms of motor neuron death by mutant TFG].
abstract: Mutations in TFG gene have been demonstrated in hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) and hereditary spastic paraplegia (HSP). A broad spectrum of TFG pathology is suspected in motor neuron diseases including amyotrophic lateral sclerosis (ALS). We performed mutation screening of TFG gene in ALS cases and evaluated the biological functions of mutant TFG by expression experiment in cultured cells. Two missense mutations associated with sporadic ALS were discovered. Mislocalization of ALS-related proteins, including TDP-43 and optineurin, was demonstrated. These results indicate that mistrafficking of ALS-related proteins by mutant TFG might be a biological cascade leading to motor neuron death.
authors.affiliation: Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Morita
authors.forename: Ryoma
authors.initials: R
authors.lastname: Morigaki
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nodera
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Goto
authors.forename: Imaharu
authors.initials: I
authors.lastname: Nakano
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D006801:Humans; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D011506:Proteins; C096163:TFG protein, human; D033921:Vesicular Transport Proteins