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Discovery of a novel aggregation domain in the huntingtin protein: implications for the mechanisms of Htt aggregation and toxicity

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Huntington's disease

Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental/ psychiatric abilities. A general lack of coordination and an unsteady gait often follow. It is also a basal ganglia disease causing a hyperkinetic movement disorder known as chorea. As the disease advances, uncoordinated, involuntary body movements of chorea become more apparent.

Silencer (genetics)

In genetics, a silencer is a DNA sequence capable of binding transcription regulation factors, called repressors. DNA contains genes and provides the template to produce messenger RNA (mRNA). That mRNA is then translated into proteins. When a repressor protein binds to the silencer region of DNA, RNA polymerase is prevented from transcribing the DNA sequence into RNA. With transcription blocked, the translation of RNA into proteins is impossible. Thus, silencers prevent genes from being expressed as proteins.

Horizontal gene transfer

Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the evolution of many organisms. HGT is influencing scientific understanding of higher order evolution while more significantly shifting perspectives on bacterial evolution.

Polyglutamine tract

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. A multitude of genes, in various eukaryotic species (including humans), contain a number of repetitions of the nucleotide triplet CAG or CAA. When the gene is translated into a protein, each of these triplets gives rise to a glutamine unit, resulting in a polyglutamine tract.

Domain name

In the Internet, a domain name is a string that identifies a realm of administrative autonomy, authority or control. Domain names are often used to identify services provided through the Internet, such as websites, email services and more. As of 2017, 330.6 million domain names had been registered. Domain names are used in various networking contexts and for application-specific naming and addressing purposes. In general, a domain name identifies a network domain or an Internet Protocol (IP) resource, such as a personal computer used to access the Internet, or a server computer.

Huntingtin

Huntingtin (Htt) is the protein coded for in humans by the HTT gene, also known as the IT15 ("interesting transcript 15") gene. Mutated HTT is the cause of Huntington's disease (HD), and has been investigated for this role and also for its involvement in long-term memory storage. It is variable in its structure, as the many polymorphisms of the gene can lead to variable numbers of glutamine residues present in the protein. In its wild-type (normal) form, the polymorphic locus contains 6-35 glutamine residues.

Top-level domain

A top-level domain (TLD) is one of the domains at the highest level in the hierarchical Domain Name System of the Internet after the root domain. The top-level domain names are installed in the root zone of the name space. For all domains in lower levels, it is the last part of the domain name, that is, the last non empty label of a fully qualified domain name. For example, in the domain name www.example.com, the top-level domain is .com.

N-terminus

The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the C-terminus, and a free amine group on the other end called the N-terminus.

Domain name registrar

A domain name registrar is a company that manages the reservation of Internet domain names. A domain name registrar must be accredited by a generic top-level domain (gTLD) registry or a country code top-level domain (ccTLD) registry. A registrar operates in accordance with the guidelines of the designated domain name registries. Until 1999, Network Solutions Inc. (NSI) operated the registries for the com, net, and org top-level domains (TLDs). In addition to the function of domain name registry operator, it was also the sole registrar for these domains.

Proteasome

Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases.