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Pathophysiological Mechanisms of Huntington’s Disease

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Book cover Pathology, Prevention and Therapeutics of Neurodegenerative Disease

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.

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Authors and Affiliations

  1. Laboratory of Translational Psychiatry, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil

    Zuleide M. Ignácio, João Quevedo & Gislaine Z. Réus

  2. Laboratory of Physiology Pharmacology and Psychopathology Campus Chapeco, Federal University of South Frontier, Chapeco, SC, Brazil

    Zuleide M. Ignácio

  3. Department of Psychiatry and Behavioral Sciences, Center for Translational Psychiatry Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    João Quevedo

  4. Department of Psychiatry and Behavioral Sciences, Center of Excellence on Mood Disorders, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    João Quevedo

  5. Neuroscience Graduate Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA

    João Quevedo

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  1. Zuleide M. Ignácio
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Editors and Affiliations

  1. Toxicology and Experimental Medicine Division, CSIR-Central Drug Research Institute, Lucknow, India

    Sarika Singh

  2. Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedar Sinai Medical Center, Los Angeles, CA, USA

    Neeraj Joshi

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Ignácio, Z.M., Quevedo, J., Réus, G.Z. (2019). Pathophysiological Mechanisms of Huntington’s Disease. In: Singh, S., Joshi, N. (eds) Pathology, Prevention and Therapeutics of Neurodegenerative Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-0944-1_5

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  • DOI: https://doi.org/10.1007/978-981-13-0944-1_5

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