Apoptosis and complement system: participating mechanisms in Huntington´s disease neurodegeneration

Abstract

The Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disease with a usual onset in the third and fourth decades of life. Occurring at an equal rate in both men and women, it presents a marked prevalence in populations of Western European origin. Clinical manifestations are progressive and include movement disorders like chorea, dementia and personality disturbances. The most striking anatomopathological characteristic is brain atrophy, predominant in the structures of the striatum (putamen, globus pallidus and caudate nucleus). Studies carried out on HD individuals led to the discovery and characterization of the huntingtin protein (HDa) whose physiological role is still unknown. Due to the mutation of the HD’s gene, IT-15, located on chromosome 4, the mutant HDa presents a polyglutamine expansion on its N-terminal extremity. Through yet unknown mechanisms, mutant HDa with polyglutamine expansion is indicated as a likely inductive factor of neurodegeneration. Occurrance of apoptosis and complement system activation, both leading to neuronal death, have been considered as responsible for clinical manifestations. This bibliographic research aims at looking into the recent hypothesis on the mechanisms involved in HD’s nerodegeneration as well as their impact on the development of future treatments.