What is a polyglutamine sequence?

A polyglutamine tract or polyQ tract is a portion of a protein consisting of a sequence of several glutamine units. A tract typically consists of about 10 to a few hundred such units.

What does huntingtin protein do?

Huntingtin is found in many of the body’s tissues, with the highest levels of activity in the brain. Within cells, this protein may be involved in chemical signaling, transporting materials, attaching (binding) to proteins and other structures, and protecting the cell from self-destruction (apoptosis).

Why does polyQ expansion cause disease?

The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative diseases that are caused by the abnormal expansion of a CAG triplet repeat (above 35–40 repeats) in the coding region within the causative gene of each disease.

What are polyglutamine diseases?

Polyglutamine diseases are a family of neurodegenerative conditions that each derive from a CAG triplet repeat expansion in a specific gene. This produces a pathogenic protein that contains a critically expanded tract of glutamines.

What is PolyQ expansion?

PolyQ diseases are characterized by the pathological expansion of CAG trinucleotide repeat in the translated region of unrelated genes. The translated polyQ is aggregated in the degenerated neurons leading to the dysfunction and degeneration of specific neuronal subpopulations.

Is Huntington’s disease autosomal dominant?

Huntington’s disease is caused by an inherited difference in a single gene. Huntington’s disease is an autosomal dominant disorder, which means that a person needs only one copy of the nontypical gene to develop the disorder.

What kind of protein is huntingtin?

Huntingtin (htt) is a soluble 3144 amino acid (348 kDa) protein, with the highest levels of expression being found in the CNS and testes. The N-terminal 17 amino acids, or N17 region, has been identified as a critical region that plays a role in htt localization, aggregation, and toxicity.

How does huntingtin protein damage cells?

There is evidence that huntingtin aggregates accumulate in the nuclei of cells, where they interfere with the process of transcription, and that they also affect other cellular processes such as axonal transport in neurons.

What is polyglutamine repeat disease?

The polyglutamine (polyQ) diseases are a group of neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding a long polyQ tract in the respective proteins.

How do trinucleotide repeats cause disease?

Depending on its location, the unstable trinucleotide repeat may cause defects in a protein encoded by a gene; change the regulation of gene expression; produce a toxic RNA, or lead to chromosome instability. In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes.

What is trinucleotide repeat disorder?

Trinucleotide repeat disorders consist of a group of human diseases, which are a result of an abnormal expansion of repetitive sequences and primarily affect the nervous system. These occur during various stages of human development.

Is Huntington’s disease a polyglutamine disease?

Huntington disease (HD) is a neurodegenerative disorder caused by expansion of polyglutamine (polyQ) repeats within the functionally enigmatic huntingtin (Htt) protein (1). The disease is characterized by movement disorder, psychiatric symptoms, and cognitive dysfunction.