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Distal hereditary motor neuronopathies (dHMNs) are a clinically and genetically heterogeneous group of disorders in which motor neurons selectively undergo age-dependant degeneration. Mutations in the small heat-shock protein HSPB1 (HSP27) are responsible for one form of dHMN. In this study, we have analysed the effect of expressing a form of mutant HSPB1 in primary neuronal cells in culture. Mutant (P182L) but not wild-type HSPB1 led to the formation of insoluble intracellular aggregates and to the sequestration in the cytoplasm of selective cellular components, including neurofilament middle chain subunit (NF-M) and p150 dynactin. These findings suggest a possible pathogenic mechanism for HSPB1 whereby the mutation may lead to preferential motor neuron loss by disrupting selective components essential for axonal structure and transport.

Original publication

DOI

10.1093/hmg/ddi452

Type

Journal article

Journal

Hum Mol Genet

Publication Date

15/01/2006

Volume

15

Pages

347 - 354

Keywords

Axonal Transport, Cells, Cultured, DNA Primers, Dynactin Complex, HSP27 Heat-Shock Proteins, Heat-Shock Proteins, Humans, Immunohistochemistry, Inclusion Bodies, Microscopy, Fluorescence, Microtubule-Associated Proteins, Mitochondria, Motor Neuron Disease, Mutation, Neoplasm Proteins, Neurofilament Proteins, Neurons