Gene therapy demonstrates that muscle is not a primary target for non-cell autonomous toxicity in familial ALS
Year: 2006
Type: article
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neuromuscular disease arising from premature death of motor neurons in the brainstem and spinal cord.Approximately 20% of familial cases of ALS are genetically linked to mutant Cu/Zn superoxide dismutase-1 (SOD1).While the hypothesis that gain of toxicity of mutant SOD1 may cause the disease is generally accepted, the ubiquitous expression of mutant SOD1 makes it hard to delineate its primary target.Previously, neither neuron specific expression nor astrocyte-specific expression provoked motor neuron degeneration.It suggested a non-cell autonomous toxicity, and the implication of multiple cell types in pathogenesis.Recent study showed that the toxicity of mutant SOD1 within motor neuron is crucial to onset and early phase of disease while mutant SOD1 within microglia accelerates disease progression.Given that deterioration of neuromuscular junction is one of earlier symptoms and the depletion or insufficient supply of various neurotrophic factors from degenerated muscle may initiate or promote motor neuron disease, mutant SOD1 damage within skeletal muscle is also a likely primary source for toxicity.This hypothesis was tested with gene therapeutic and genetic approaches.Even though viral delivered siRNA (short interfering RNA) against mutant SOD1 into I wish to thank my adviser, Brian K. Kaspar.His scientific guidance, patience, commitment, and contagious goodwill allowed me to complete my Ph D. study.Also, I'd like to thank Hannah Arnson for helping the analysis of muscle pathology and animal behavior study.I also wish to thank Dr. Don W. Cleveland and Fred H. Gage for discussion and critical review.I am grateful to Ji-sun Lee, So-young Lim, Jimi Nickel, Emily Erdman, Jae-Woo Lee, Chae-Eun Lim for their friendship and motivation.Without their encouragement and care, my Ph D. study would have been very difficult.Most importantly, I want to thank my Mom and Dad for their understanding
Author: Soo Hyun Kim
Institution: The Ohio State University
Language: German
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2403607898