Huntington 's Disease : An Autosomal Recessive Autosomal Dominant Autosomal Disorder

2037 WordsDec 5, 20149 Pages
Abstract Huntington’s disease is an autosomal, dominant inherited disorder caused by a polyglutamine expansion at the amino-terminal on the huntingtin protein. It causes a progressive degeneration of spiny nerve cells in the striatum and cortex of the brain, impairing a person’s functional and cognitive abilities. Polyglutamine repeats of 36 are found to be non-threating but sequences containing an additional two or three repeats are associated with Huntington’s disease. According to aggregation kinetics, the rate of aggregation formation is dependent upon the amount of polyglutamine polypeptides. Aggregates in Huntington’s disease are formed from the mutant huntingtin fragments when the protein is cleaved at the N-terminal. This occurs after a conformation change into a β-sheet conformation. Huntingtin is cleaved by caspase, known for apoptosis, and calpain. Cleavage at caspase-3 sites and inhibited cleavage caspase-6 sites did not produce Huntington’s disease characteristics. Mutant huntingtin proteins contain more active calpains because of the increase in neurotransmitter – glutamate – release, enhancing NMDA-receptor activity. An increased glutamate level on spiny neurons was found to increase apoptosis in nerve cells. There are currently no treatment or cures for Huntington’s disease. However, new therapy ideas are centered on the inhibition of proteolytic cleavage. Introduction Huntington’s disease is an autosomal, dominant inherited disorder. It causes
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