AIF translocates to the nucleus in the spinal motor neurons in a mouse model of ALS.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons in the brain stem and the spinal cords. One of the causes for the familial ALS has been attributed to the mutations in copper-zinc superoxide dismutase (SOD1). Although the toxic function of the mutant enzyme has not been fully understood, the final cell death pathway has been suggested as caspase-dependent. In the present study, we present evidence that the activation of apoptosis inducing factor (AIF) may play a role to induce motor neuron death during ALS pathogenesis. In the spinal cord of SOD1 G93A transgenic mice, expression of AIF was detected in the motor neurons and astrocytes. The level of AIF expression increased as the disease progressed. In the symptomatic SOD1 G93A transgenic mice, AIF released from the mitochondria and translocated into the nucleus in the motor neurons as evidenced by confocal microscopy and biochemical analysis. These results suggest that AIF may play a role to induce motor neuron death in a mouse model of ALS.
Oh
Yeo Kyoung
YK
Department of Molecular Biology, Sejong University, 98 Gunja-Dong, Kwangjin-Gu, Seoul, Republic of Korea.
Shin
Ki Soon
KS
Kang
Shin Jung
SJ
D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002467:Cell Nucleus / Q000378:metabolism*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics
D051033:Apoptosis Inducing Factor; D005904:Glial Fibrillary Acidic Protein; C494830:AIFM1 protein, mouse; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase