Probing Neurodegeneration

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Science  18 May 2007:
Vol. 316, Issue 5827, pp. 955
DOI: 10.1126/science.316.5827.955b

Although great strides have been made toward the global eradication of poliovirus, this pathogen continues to be studied intensely in research labs, in part because history has shown that identification of the cellular pathways disrupted by viruses can provide fundamentally important insights into disease. One mystery yet to be solved is how poliovirus causes the motor neuron degeneration that leads to the muscle weakness and paralysis typical of poliomyelitis.

A tantalizing clue has emerged from the work of Almstead and Sarnow, who have identified a potentially unifying molecular feature of poliomyelitis and spinal muscular atrophy, an inherited neurodegenerative disease. Spinal muscular atrophy arises from loss or mutational inactivation of the gene encoding the survival of motor neurons (SMN) protein. Together with eight other proteins called Gemins, SMN is part of a dynamic macromolecular complex that facilitates the assembly of ribonucleoprotein complexes implicated in pre-mRNA splicing. The splicing complexes are built around a so-called Sm core of RNA-binding proteins, and patients with spinal muscular atrophy show reduced levels of Sm core assembly. The authors show that poliovirus infection inhibits Sm core assembly through viral-mediated proteolysis of Gemin3, a critical component of the SMN complex. The downstream effects of reduced Sm core formation on motor neuron survival have been contentious, but poliovirus may serve as a useful research tool for exploring this issue. — PAK

Genes Dev. 21, 1086 (2007).

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