Huntington’s disease: Believe, Hope and Faith to cure this Invisible Disability
Huntington’s disease
Huntington’s disease

Neuron holds an important part in human body. It is as important as if it stops working mechanism of human body get disturbed. Commonly known as neuron and nerve cell, is an electrically excitable celled that receives the information process it and transmit through electrical and chemical signal. These signals are transferred through specialized connection known as synapses. Being a primary component of nervous system which includes brain and spinal cord and of the peripheral nervous system holds an importance in human life.

Progressive loss of structure or functioning of neuron including death of neuron is common and known as Neurodegeneration.  Many neurodegenerative diseases like amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease arise as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration or death of neuron cells. Neurodegeneration can be traced in many different levels of neuronal circuitry ranging from molecular to systemic.

Huntington disease (HD) is a seldom found neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, and psychiatric disturbances. One out of ten thousand populations is estimated to suffer from Huntington disease. Mean age at onset of symptoms is 30-50 years. Huntington’s disease (HD) is caused by a dominant mutation in HTT, the HD gene.

Cause of Huntington’s disease

Dominantly inherited disease HD is caused, in most cases, by an expansion of a CAG repeat located in the DNA encoding the first exon of HTT. Most diseased person with HD carries only one disease-causing mutant allele. The HD gene is located on the distal arm of chromosome. Most disease-causing alleles of the HD gene occur on a common haplotype that is relatively rare in individuals of European descent and absent from several populations of Asian and African origins.

Reason behind the Abnormality

The HD gene encodes a large, 3144 amino acid long protein called ‘Huntingtin’, with roles in a variety of cellular functions, prominent among which are vesicle trafficking, energy production and transcription. The CAG repeat in the HD gene encodes a stretch of glutamine residues in the N-terminus of Huntingtin, beginning after the 17th amino acid. In control populations, the CAG repeat averages between 17 and 20 units long. Individuals with repeats of ≥40 units are at risk for HD and can expect to develop disease phenotypes if they live a normal-length life, i.e. the penetrance of such mutations is considered to be 100%. It is also known that longer repeats confer, on the average, earlier ages of symptom onset. Individuals with 36–39 CAG repeats are at risk for developing HD though the penetrance is reduced.

The mechanism by which the expressed expanded CAG repeat in HTT causes HD is only poorly understood. Though most investigators consider the mutant Huntingtin protein with its expanded glutamine stretch the prime culprit, toxicity resulting from triplet repeat-containing RNAs and/or dysregulation of antisense transcripts has not been fully explored. The expression of long glutamine tracts either alone, in the context of an N-terminal fragment or full-length Huntingtin protein, or inserted into other proteins has been shown to disrupt a wide variety of biological functions in cells and model organisms. Nonetheless, which disruptions in which cells lead to the phenotype of HD remain unsettled.

Symptoms and Stages of the Disease

In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington’s disease; JHD). The classic sign is chorea that gradually spreads to all muscles.

If the first symptoms and signs start before or at the age of 20 years, the disease is called Juvenile Huntington’s disease (JHD). Behavior and learning difficulties at school are often the first signs. In 80% of the juveniles the father is the affected parent.

HD is a shattering disease caused, in the vast majority of cases, by a genetic mutation that is readily identified independent of the onset of disease symptoms. However, understanding the molecular and cellular pathogenic mechanisms that underlie the development of disease phenotypes remains a significant challenge, principally because it presumes an understanding of the molecular and cellular mechanisms that underlie normal functioning in humans, which, at the moment, is significantly incomplete. Nonetheless, efforts to develop therapies based on silencing the expression of the HD gene, though clearly a technical challenge, seem poised for success. Furthermore, identification of compounds that act to reduce the amount of mutant hunting tin protein in cell-based or model organism screens may also yield useful therapeutic leads.

Additional lines of research that are extensively designed to yield therapies for HD are likely to entail experiments that provide validation of pathogenic mechanisms. In most cases, this will involve in vivo genetic experiments.

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