Publication Date:
2006-06-03
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boillee, Severine -- Yamanaka, Koji -- Lobsiger, Christian S -- Copeland, Neal G -- Jenkins, Nancy A -- Kassiotis, George -- Kollias, George -- Cleveland, Don W -- MC_U117581330/Medical Research Council/United Kingdom -- NS 27036/NS/NINDS NIH HHS/ -- R37 NS027036/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2006 Jun 2;312(5778):1389-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16741123" target="_blank"〉PubMed〈/a〉
Keywords:
Amyotrophic Lateral Sclerosis/*enzymology/genetics/pathology/physiopathology
;
Animals
;
Antigens, CD11b/genetics
;
Disease Progression
;
Female
;
Humans
;
Integrases/genetics
;
Male
;
Mice
;
Mice, Inbred C57BL
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Mice, Transgenic
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Microglia/*metabolism
;
Motor Neurons/*metabolism
;
Mutation
;
Superoxide Dismutase/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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