Onset and progression in inherited ALS determined by motor neurons and microglia

Séverine Boillée, Koji Yamanaka, Christian S. Lobsiger, Neal G. Copeland, Nancy A. Jenkins, George Kassiotis, George Kollias, Don W. Cleveland

Research output: Contribution to journalArticle

1162 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1389-1392
Number of pages4
JournalScience
Volume312
Issue number5778
DOIs
StatePublished - Jun 2 2006

ASJC Scopus subject areas

  • General

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