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Pathophysiological Mechanisms of Huntington’s Disease

  • Zuleide M. Ignácio
  • João Quevedo
  • Gislaine Z. Réus
Chapter

Abstract

Huntington’s disease (HD) is a dominant autosomal monogenic disease whose pathophysiological basis comes from a mutation in the huntingtin (HTT) protein. HTT is one of the proteins whose gene has a polymorphic CAG trinucleotide repeat tract, leading to the formation of polyglutamine tract in the N-terminal region of the protein. The expansion of CAG repeat is the basic characteristic of mutated huntingtin (mHTT). HD is therefore characterized as one of the polyglutamine diseases (PolyQ). The initially apparent main symptoms are motor changes, with choreic movements, progressive loss of motor coordination, cognitive decline, and psychiatric disorders. The pathophysiology of this disease involves a wide range of biological mechanisms, whose alterations culminate in gliosis, with loss of astrocytes and oligodendrocytes, and in neuronal death and atrophy of brain tissues, with the most affected regions starting with the striatum, which integrates circuit of the basal ganglia and the cerebral cortex. Medium-sized spiny projecting neurons which release inhibitory γ-aminobutyric acid (GABA) neurotransmitter are the most affected, but many other neurons and neurotransmitters are involved in the circuit dysfunction. Among biological alterations inherent or consequent to the dysfunctions in the neurotransmission system are cellular inclusions of protein aggregates, changes in cellular signaling pathways, energy metabolism, oxidative balance, and inflammatory mechanisms. This chapter discourse some well-defined basic pathophysiological features and some mechanisms that are the most recent study objects in HD.

Keywords

Pathophysiology Genetics Neurotransmission Oxidative stress Neuroinflammation Huntington’s disease 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Zuleide M. Ignácio
    • 1
    • 2
  • João Quevedo
    • 1
    • 3
    • 4
    • 5
  • Gislaine Z. Réus
    • 1
  1. 1.Laboratory of Translational Psychiatry, Graduate Program in Health Sciences, Health Sciences UnitUniversity of Southern Santa CatarinaCriciumaBrazil
  2. 2.Laboratory of Physiology Pharmacology and Psychopathology Campus ChapecoFederal University of South FrontierChapecoBrazil
  3. 3.Department of Psychiatry and Behavioral SciencesCenter for Translational Psychiatry Medical School, The University of Texas Health Science Center at HoustonHoustonUSA
  4. 4.Department of Psychiatry and Behavioral SciencesCenter of Excellence on Mood Disorders, Medical School, The University of Texas Health Science Center at HoustonHoustonUSA
  5. 5.Neuroscience Graduate ProgramGraduate School of Biomedical Sciences, The University of Texas Health Science Center at HoustonHoustonUSA

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