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  • Title: Apoptosis-inducing factor and cyclophilin A cotranslocate to the motor neuronal nuclei in amyotrophic lateral sclerosis model mice.
    Author: Tanaka H, Shimazaki H, Kimura M, Izuta H, Tsuruma K, Shimazawa M, Hara H.
    Journal: CNS Neurosci Ther; 2011 Oct; 17(5):294-304. PubMed ID: 20553309.
    Abstract:
    AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease whose mechanism is not understood. Recently, it was reported that apoptosis-inducing factor (AIF) was involved in motor neuronal cell death in ALS model mice, and AIF-induced neuronal cell death by interacting with cyclophilin A (CypA). However, it is unknown whether the CypA and AIF-complex induces chromatinolysis in ALS. Therefore, in the present study, we investigated the process of motor neuron degeneration as the disease progresses and to determine whether the CypA-AIF complex would play a role in inducing motor neuronal cell death in mutant superoxide dismutase 1 (SOD1)(G93A) ALS model mice. METHODOLOGY: We prepared the nuclear fractions of spinal cords and demonstrated the nuclear translocation of CypA with AIF in SOD1(G93A) mice by immunoprecipitation. The localization of CypA and AIF in the spinal cords was assessed by immunohistochemistry. RESULTS: In the spinal cords of SOD1(G93A) mice, the expressions of CypA and AIF were detected in the motor neurons, and CypA and AIF cotranslocated to the motor neuronal nuclei with CypA. Furthermore, the expression of CypA was detected in GFAP-positive astrocytes, but not in CD11b-positive microglial cells. On the other hand, these findings were not detected in the spinal cords of wild-type mice. CONCLUSIONS: From these results, we suggest that CypA and AIF may play cooperative and pivotal roles in motor neuronal death in the murine ALS model.
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