Androgen receptor function in motor neuron survival and degeneration.
Polyglutamine repeat expansion in the androgen receptor is responsible for the motor neuron degeneration in X-linked spinal and bulbar muscular atrophy (SBMA; Kennedy's disease). This mutation, like the other polyglutamine repeat expansions, has proven to be toxic itself by a gain-of-function effect; however, a growing body of evidence indicates that loss of androgen receptor normal function simultaneously contributes to SBMA disease pathology, and, conversely, that normal androgen receptor signaling mediates important trophic effects upon motor neurons. This review considers the trophic requirements of motor neurons, focusing upon the role of known neurotrophic factors in motor neuron disease natural history, and the interactions of androgen receptor signaling pathways with motor neuron disease pathogenesis and progression. A thorough understanding of androgen receptor signaling in motor neurons should provide important inroads toward the development of effective treatments for a variety of devastating motor neuron diseases.
Cary
Gregory A
GA
Department of Laboratory Medicine, University of Washington Medical Center, Box 357110, Room NW 120, Seattle, WA 98195-7110, USA.
La Spada
Albert R
AR
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction
D011944:Receptors, Androgen