The chances of developing cancer are lower in patients suffering from Huntington’s disease and other polyQ or polyglutamine diseases. Polyglutamine (polyQ) disorders are inherited neurodegenerative diseases and are caused by polyQ expansion in the mutant proteins. The patient shows comparable retinal neurodegeneration, characterized by morphological and functional alterations of rod photoreceptors. Transcriptional deregulations are also seen in polyQ diseases; however, their relationship with the neurodegenerative processes is not well defined. At the mid-stage of the disease, where there is no significant cell loss, Gene Chips expression analysis and additional validations reveal a broad down-regulation of genes involved in rod morphogenesis and photo transduction function. Consistently, transcription factors controlling these genes and maintaining rod differentiation are repressed.
Moreover, factors having inhibitory effect on photoreceptor differentiation are up-regulated. These indicate that independently from the protein context, polyQ expansion overrides the genetic control of photoreceptor differentiation, leading to rod dysfunction. To define the molecular pathways that trigger later cell death in these dysfunctional, non-differentiated rod photoreceptors is important. Cell cycle reactivation seems to drive post-mitotic neurons to death, in other neurodegenerative diseases, such as Alzheimer’s disease. Alterations of many cell cycle regulators, at late stage of the disorder are found, suggesting that aberrant cell cycle reentry is responsible for cell death. PolyQ pathogenesis is associated with loss of differentiation state in affected neurons, revealing new potential therapeutically strategies. The nine diseases that have been identified include Dentatorubral, Huntington’s disease (HD), Pallidoluysian atrophy, Spinobulbar muscular atrophy (SBMA) and 6 types of spinocerebellar ataxia.
Out of these Huntington’s disease is common. In this disease the patients’ muscle coordination is affected; there are also cognitive decline and psychiatric problems. Signs and symptoms become more apparent during mid-adulthood. Neurologists say Huntington’s disease is the most common genetic cause of chorea – abnormal involuntary writhing movements. The disease used to be called Huntington’s chorea. All polyQ disorders present with progressively worsening degeneration of a group of neurons in the CNS (central nervous system) that regulate motor control. The development of cancer in patients with polyQ disorders is blocked. Huntington’s disease patients have a 53% lower chance of developing cancer compared to the general population and spinobulbar muscular atrophy patients have a 35% lower chance of developing cancer. Also, hereditary ataxia patients have a 23% lower chance of developing cancer. Thus, a common mechanism is seen in patients with polyQ diseases that protects against the development of cancer. However, specific biological mechanisms underlying the reduced cancer risk in patients with polyQ diseases still need to be investigated.