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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




Journal article


Hum Mol Genet

Publication Date





347 - 354


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, Molecular Chaperones, Motor Neuron Disease, Mutation, Neoplasm Proteins, Neurofilament Proteins, Neurons