Exp Neurobiol 2015; 24(3): 226-234
Published online September 30, 2015
© The Korean Society for Brain and Neural Sciences
Do-Yeon Lee1#, Gye Sun Jeon1,2#, Yu-mi Shim1, Seung-Yong Seong3, Kwang-Woo Lee1 and Jung-Joon Sung1*
1Department of Neurology, 2Biomedical Research Institute, Seoul National University Hospital College of Medicine, 3Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2072-1015, FAX: 82-2-3672-7553
#These authors contributed equally to this work.
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by selective degeneration of motor neurons. Mutant superoxide dismutase 1 (SOD1) is often found as aggregates in the cytoplasm in motor neurons of various mouse models and familial ALS patients. The interplay between motor neurons and astrocytes is crucial for disease outcome, but the mechanisms underlying this phenomenon remain unknown. In this study, we investigated whether transient transfection with wild-type and mutant-type SOD1 may lead to amplification of mutant SOD1-mediated toxicity in cortical neurons and astrocytes derived from wild-type and mutant-type (human G93A-SOD1) mice. In transgenic mice expressing either wild- or mutant-type SOD1, we found that green fluorescent protein (GFP)-wtSOD1 was present in the cytoplasm and nuclei of wild-type cortical neurons and astrocytes, whereas GFP-mutant SOD1 was mainly cytoplasmic in wild- and mutant-type cortical neurons and astrocytes. These findings indicate that intracellular propagation of misfolding of GFP-wt or mtSOD1 are possible mediators of toxic processes involved in initiating mislocalization and aggregation. Here, we provide evidence that cytoplasmic aggregates induce apoptosis in G93A-SOD1 mouse cortical neurons and astrocytes and that the toxicity of mutant SOD1 in astrocytes is similar to the pathological effects of ALS on neurons
Keywords: Amyotrophic lateral sclerosis, cortical astrocyte, cortical neuron, G93A SOD1, mislocalization, apoptosis