How many proteins does huntingtin interact with?
How many proteins does huntingtin interact with?
Huntingtin mediated trafficking of vesicles and organelles. Htt, with its large number of protein-protein interaction domains, has been found to interact so far with over 200 other proteins [45, 46, 91, 92].
How does Huntington’s disease affect the huntingtin protein?
Htt is a huge cytosolic protein (3144 amino acids) associated with Huntington’s disease. The abnormal polyglutamine expansion in the N-terminal region of Htt produces significant dysfunction and neural death, especially in the medium spiny neurons of the striatum (Kremer et al., 1994).
What protein is misfolded in Huntington’s disease?
Huntington’s disease, a lethal neurodegenerative condition, is believed to be caused by misfolding of mutated versions of huntingtin protein in which a glutamine-containing sequence is repeated too many times.
What is polyglutamine aggregation?
The appearance of polyglutamine (polyQ)-containing aggregates [1–3] is a hallmark of disease progression in all diseases in which CAG-expansions occur in genes [2]. Intranuclear inclusion bodies containing polyQ aggregates have been found in vitro [4,5], in cell cultures, animal models, and affected patients [6,7].
What does the 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).
What does mutated huntingtin protein do?
Although the signaling pathways involved in HD are not yet clearly elucidated, mutant huntingtin protein is a key factor in the induction of neurodegeneration. The mutant huntingtin protein alters intracellular Ca2+ homeostasis, disrupts intracellular trafficking and impairs gene transcription.
What does a normal huntingtin protein do?
Normal Function 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).
How does the misfolding of proteins cause Alzheimer’s?
Alzheimer’s disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded Amyloid-beta proteins in the brains of AD patients.
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. Important examples of polyglutamine diseases are spinocerebellar ataxia and Huntington’s disease.
What are the glutamine repeats in huntingtin protein?
In contrast, altered HD huntingtin protein (called “ Htt ” by researchers), contains 40 or more glutamine repeats, resulting from the genetic mutation discussed above. The extended number of glutamine repeats in Htt characterizes HD as one of nine polyglutamine expansion disorders. (To read more about these disorders, click here .)
How does huntingtin aggregates cause cell dysfunction in HD?
Researchers have explored a number of hypotheses regarding the mechanisms by which huntingtin aggregates cause cell dysfunction in HD. Recent studies have shown that altered huntingtin can “kidnap” smaller proteins from their usual locations, preventing them from functioning normally within nerve cells.
What makes up the product of the gene huntingtin?
The order of these bases determines the protein “product” of the gene. (To read more about DNA, click here .) Everyone has a gene that codes for huntingtin protein, a protein found in the cells of the body, which we will discuss later. Towards the beginning of this gene, the three-letter codon sequence C-A-G is repeated a few times.
How are protein aggregation and inclusion body formation related?
Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and prion diseases are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation.