Rinsho Shinkeigaku (Clinical Neurology)

Symposium 3

Pathomechanisms of motor neuron death by mutant TFG

Toshitaka Kawarai, M.D.1), Mitsuya Morita, M.D.2), Ryoma Morigaki, M.D.3), Koji Fujita, M.D.1), Hiroyuki Nodera, M.D.1), Yuishin Izumi, M.D.1), Satoshi Goto, M.D.3), Imaharu Nakano, M.D.4) and Ryuji Kaji, M.D.1)

1)Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School
2)Department of Neurology, Jichi Medical School
3)Department of Motor Neuroscience and Neurotherapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School
4)Tokyo Metropolitan Neurological Hospital

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.
Full Text of this Article in Japanese PDF (530K)

(CLINICA NEUROL, 53: 1199|1199, 2013)
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(Received: 31-May-13)