Huntington’s Disease

A Review on the Physiopathological Aspects

Abstract

Introduction. Huntington’s disease (HD) is a brain neurodegenerative disorder, characterized by the loss of motor coordination, psychiatric disturbances, cogniticve decline and progressive dementia. HD is caused by a mutation in the gene encoding for a protein normally present in the human body, huntingtin. At the cerebral level, mutant huntingtin causes the selective death of striatal, cortical and hypothalamic neurons. The mutation underlies changes in several basic intracellular mechanisms that lead to dysfunction of nigro- and corticostriatal pathways. Objective. The goal of this study is to present a critical overview of the main mechanisms responsible for the glutamatergic and dopaminergic dysfunction, as well as the pathways involved in metabolic and mitochondrial dysfunction in HD. Method. We performed a PubMed search and selected scientific articles that were published since 1980. Results. We selected 10 review articles and 85 original articles, all published in English. Conclusion. Based on the literature, it is possible to conclude that mutant huntingtin-induced neuronal dysfunction occuring outside the striatum (namely in the cortex and substantia nigra) plays a critical role during the initial stages of the disease. This information may be relevant for the development of new therapeutic strategies for HD.