Huntington’s disease: the coming of age

Abstract

Huntington's disease (HD) is caused due to an abnormal expansion of polyglutamine repeats in the first exon of huntingtin gene. The mutation in huntingtin causes abnormalities in the functioning of protein, leading to deleterious effects ultimately to the demise of specific neuronal cells.The disease is inherited in an autosomal dominant manner and leads to a plethora of neuropsychiatric behaviour and neuronal cell death mainly in striatal and cortical regions of the brain, eventually leading to death of the individual. The discovery of the mutant gene led to a surge in molecular diagnostics of the disease and in making different transgenic models in different organisms to understand the function of wild-type and mutant proteins. Despite difficult challenges, there has been a significant increase in understanding the functioning of the protein in normal and other gain-of-function interactions in mutant form. However, there have been no significant improvements in treatments of the patients suffering from this ailment and most of the treatment is still symptomatic. HD warrants more attention towards better understanding and treatment as more advancement in molecular diagnostics and therapeutic interventions are available. Several different transgenic models are available in different organisms, ranging from fruit flies to primate monkeys, for studies on understanding the pathogenicity of the mutant gene. It is the right time to assess the advancement in the field and try new strategies for neuroprotection using key pathways as target. The present review highlights the key ingredients of pathology in the HD and discusses important studies for drug trials and future goals for therapeutic interventions.

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

“…The mutation inside this gene leads to bad protein production which ultimately causes the symptoms of the disease such as choreic movement and troubles in cognitive and emotional feelings. HD leads to death in most of the patients (131,172,173). Lack of a suitable conventional therapy is a characteristic shared between most of the neurodegenerative diseases such as HD.…”

Escins Isolated from Aesculus chinensis Bge. Promote the Autophagic Degradation of Mutant Huntingtin and Inhibit its Induced Apoptosis in HT22 cells

“…Autophagy plays an important role in maintaining cellular homeostasis by degrading damaged or unnecessary materials in cells (Mizushima and Komatsu, 2011;Gitler et al, 2017;Yu et al, 2017;Pandey and Rajamma, 2018). Intracytoplasmic aggregateprone proteins such as b-amyloid (Ab), hyperphosphorylated tau, mutant a-synuclein and huntingtin rapidly accumulate as autophagy is impaired in cellular and animal models (Kampmann, 2017;Wu et al, 2018).…”

“…However, it causes many adverse effects, such as significant depression, lethargy and Parkinsonian syndrome occurrence. Recently, many compounds and natural products have been reported to degrade mHtt via autophagy (Dayalu and Albin, 2015;Wyant et al, 2017;Pandey and Rajamma, 2018). For example, rilmenidine, a U.S. Food and Drug Administration (FDA) approved drug, was reported to induce autophagy and attenuate the cytotoxicity induced by mHtt.…”

Incidence of Huntington disease in a northeastern Spanish region: A 13-year retrospective study at tertiary care centre

“…Huntington's disease (HD) is a progressive neurodegenerative disorder caused by the anomalous expansion of polyglutamine repeats (encoded by the trinucleotide CAG, Cytosine-Adenine-Guanine) in the rst exon of the huntingtin gene (HTT, also known as HD or IT15 gene), located in the short arm of chromosome 4 (4p16.3) (OMIM#143100) [1].…”