Molecular pathogenesis of peripheral neuropathies: insights from Drosophila models

Peripheral neuropathies are characterized by degeneration of peripheral motor, sensory and/or autonomic axons, leading to progressive distal muscle weakness, sensory deficits and/or autonomic dysfunction. Acquired peripheral neuropathies, e.g., as a side effect of chemotherapy, are distinguished from inherited peripheral neuropathies (IPNs). Drosophila models for chemotherapy-induced peripheral neuropathy and several IPNs have provided novel insight into the molecular mechanisms underlying axonal degeneration. Forward genetic screens have predictive value for discovery of human IPN genes, and the pathogenicity of novel mutations in known IPN genes can be evaluated in Drosophila. Future screens for genes and compounds that modify Drosophila IPN phenotypes promise to make valuable contributions to unraveling the molecular pathogenesis and identification of therapeutic targets for these incurable diseases.