Document Type : Review Article

Authors

1 Department of Biochemistry, University of Nigeria, Nsukka, Enugu, Nigeria

2 Department of Community Health Extension, School of Public Health/Nursing Technology, Nsukka, Enugu, Nigeria

3 Department of Applied Sciences, Federal College of Dental Technology and Therapy, Enugu, Nigeria

10.22034/jcr.2023.362508.1194

Abstract

One of the leading causes of death apart from cancer is a neurodegenerative disease. Huntington's disease (HD) is such that affects the neurons resulting from the programmed degeneration of the nerve cells. It is expressed throughout the brain, most striking within the striatum and the cortex. The misfolded HD protein interrupts the other interacting proteins' activity resulting in the abnormal functioning of the nerve cells leading to the uncontrolled movements, loss of intellectual faculties, emotional disturbances categorizing motor dysfunctions, and behavioural and cognitive deficits. The genomic origin of the disease can be traced to the amplification of a cysteine-adenosine-guanine repeat that encodes a polyglutamine region in the huntingtin’s amino terminal end. However, the mechanism and modality in which cysteine-adenosine-guanine expansion leads to a poisonous effect on the neuron are yet to be clearly understood. However, studies have recently revealed that change in the blueprint (mRNA) of the protein gives rise to misfolded protein and the fragments accumulate, by making interaction with the other elements in cells resulting in the problems associated with HD. Hence, as opposed to the traditional and controversial protein misfolding hypothesis, amyloid formation is the result rather than the HD cause. Although, the N-terminal fragments of mutant huntingtin (mHtt) misfolded into amyloid-like fibrils as a key signature of HD pathology. Currently, no effective remedy has been found for HD. This review highlights the possible cause, pathogenesis, and recent therapy aiming at down-regulating the expression of huntingtin (Htt), lowering the misfolding, and aggregation of the huntingtin protein. 

Graphical Abstract

Huntington Disease: Mechanism of Pathogenesis and Recent Developments in Its Therapeutic Strategies-A Short Review

Keywords

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