| Popis: |
This chapter discusses clinical features and molecular biology of Kennedy's disease. Kennedy's disease, also known as spinal and bulbar muscular atrophy (SBMA), is an X-linked motor neuron disease caused by GAG repeat expansion in the androgen receptor gene, resulting in polyglutamine tract expansion in the receptor protein. Affected males develop a chronic, progressive neuromuscular deficit and may also show signs of androgen insensitivity. As in other polyglutamine diseases, a pathological feature is inclusion formation in cells expressing the mutant protein. Unlike most other polyglutamine disorders, the normal function of the mutant protein in SBMA is well known. The mutation leads to both a toxic gain of function in affected cells, and a loss of normal receptor function. Lower motor neurons in the spinal cord and brainstem express high levels of the androgen receptor, and these are the cells most susceptible to degeneration in SBMA. In cell culture and animal models, expression of mutant receptor leads to motor neuron dysfunction and cell death. Binding of androgen to the mutant receptor protein has been shown to be important in the pathogenesis of SBMA. There is currently no specific treatment for this disease. However, antiandrogen treatment has been found to be effective in animal models, and is currently being tested in patients with SBMA. |
