alexa Onset and progression in inherited ALS determined by motor neurons and microglia.
Neurology

Neurology

Journal of Alzheimers Disease & Parkinsonism

Author(s): Boille S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA,

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Abstract Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), a progressive paralytic disease characterized by loss of motor neurons. With the use of mice carrying a deletable mutant gene, expression within motor neurons was shown to be a primary determinant of disease onset and of an early phase of disease progression. Diminishing the mutant levels in microglia had little effect on the early disease phase but sharply slowed later disease progression. Onset and progression thus represent distinct disease phases defined by mutant action within different cell types to generate non-cell-autonomous killing of motor neurons; these findings validate therapies, including cell replacement, targeted to the non-neuronal cells. This article was published in Science and referenced in Journal of Alzheimers Disease & Parkinsonism

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