Two Cell Types Play Role in Amyotrophic Lateral Sclerosis

SOD1 mutations have distinct effects on neurons and microglia that control different aspects of disease

THURSDAY, June 1 (HealthDay News) -- Two separate cell types in the nervous system may be responsible for the progression of amyotrophic lateral sclerosis caused by dominant mutations in the superoxide dismutase (SOD1) gene, according to a report in the June 2 issue of Science. The findings have important implications for therapeutic targeting, the authors report.

To determine how mutant SOD1 expression in either neurons or microglia influence disease progression, Severine Boillee, Ph.D., from the University of California San Diego, and colleagues used a transgenic mouse expressing mutant SOD1 that can be silenced in specific cell types of their progeny by mating with another transgenic mouse expressing a control element in the targeted tissue.

The researchers found the presence of mutant SOD1 in neurons was a primary determinant of disease onset and early phase disease progression. However, the disease progressed more quickly when the mutant was also expressed in the microglia. The investigators believe this represents two phases of disease progression controlled by the separate cell types.

"In our study, limiting mutant damage to microglia robustly slowed the disease's course, even when all motor neurons were expressing high levels of a SOD1 mutant," the authors write. "Thus, although the initiation of the disease requires damage to motor neurons and probably to additional cell types, disease therapy might be successful by targeting only a single non-neuronal cell type."

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Barry Thrash

Barry Thrash

Updated on June 01, 2006

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