Exp Neurobiol.
2015 Sep;24(3):226-234. 10.5607/en.2015.24.3.226.
Modulation of SOD1 Subcellular Localization by Transfection with Wild- or Mutant-type SOD1 in Primary Neuron and Astrocyte Cultures from ALS Mice
- Affiliations
-
- 1Department of Neurology, Seoul National University Hospital College of Medicine, Seoul 03080, Korea. jjsaint@snu.ac.kr
- 2Biomedical Research Institute, Seoul National University Hospital College of Medicine, Seoul 03080, Korea.
- 3Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
- KMID: 2165559
- DOI: http://doi.org/10.5607/en.2015.24.3.226
Abstract
- 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 in vitro. Collectively, our results indicate that mtSOD1 probably interacts with wtSOD1 via an unknown mechanism to produce augmented toxicity and may influence aggregate formation and apoptosis.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Impairment of Neurite Formation in Familial ALS-associated Cu, Zn-Superoxide Dismutase Mutant Cells
- Region-specific changes in the immunoreactivity of Atg9A in the central nervous system of SOD1(G93A) transgenic mice
- Clinical Characteristics of Korean Juvenile Amyotrophic Lateral Sclerosis
- Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis
- Selective Cytotoxic Mechanism of Homocysteine to Motor Neuronal Cells Expressing the Mutant Cu,Zn-superoxide Dismutase
