HD Glossary

Note: Some words can have differing definitions depending on the context in which they are used. The definitions presented here are the ones that best apply to the words as they are used. HDSA is grateful to the Stanford Hopes website for their contribution and maintenance of this glossary.

 

 

H
  • half-life - The half-life of a substance is the amount of times it takes for half of the original molecule to be chemically degraded or eliminated in some other way (for example, in the urine). For example; if the half life of a compound is 5 hours, there will be 50% left at 5 hours, 25% of the original amount left at 10 hours, and 12.5% left after 15 hours.
  • hairpin - A section of single-stranded DNA that curls back onto itself, creating a partial double helix that resembles a hairpin.
  • hairpin-mediated polymerase slippage model - A possible explanation for why expansions occur. This model expands on the polymerase slippage model and shows how hairpins make long-range polymerase slippage energetically feasible.
  • HAP-1 - huntingtin-associated protein-1. A cytoplasmic protein (associated with the membrane cytoskeleton) that is expressed predominantly in the brain. HAP-1 is expressed in many neurons. Expanded CAG repeats in the huntingtin protein show increased binding to HAP-1.
  • haploid - Containing one set of chromosomes. Gametes are haploid cells.
  • haplotype - The genetic makeup of an individual with respect to a specific pair of alleles or genes.
  • HD allele - A version of the Huntington gene that contains a higher than normal number of repeats. Individuals with the HD allele will develop Huntington’s disease (Note that although there are many different alleles that can cause HD, for simplicity, this site refers to any allele that causes HD as "the HD allele.") This allele may be called the “mutant Huntington allele” in other places. See Table A-1.
  • HDAC - Abbreviation for histone deacetylase.
  • HDAC inhibitors - Abbreviation for histone deacetylase inhibitors.
  • HDBP1 - Abbreviation for Huntington’s Disease Binding Protein 1, a protein that binds to the promoter region of the Huntington gene, leading to transcription of the HD allele. The allele, in turn, gives rise to the huntingtin protein.
  • HDBP2 - Abbreviation for Huntington’s Disease Binding Protein 2, a protein that binds to the promoter region of the Huntington gene, leading to transcription of the HD allele. The allele, in turn, gives rise to the huntingtin protein.
  • HDJ1 - A human protein that is known to exert protective effects against polyglutamine toxicity.
  • HD Motor Rating Scale (HDMRS) - A rating system designed to measure the motor capacity of people with HD. It consists of 14 items that are specific to the motor symptoms that are typically exhibited by people with HD.
  • HDSA Center of Excellence - Clinics recognized by HDSA for providing high quality, comprehensive care for HD patients and their families and for offering clinical trial opportunities and running outreach and educational programs.
  • heart attack - Heart attacks occur when a coronary artery is completely blocked and a portion of the heart muscle is left without a supply of oxygenated blood. If the portion is large enough, the heart attack may be deadly.
  • heart disease - A general term for high blood pressure and/or the narrowing of arteries supplying blood to the heart; the most common cause of death in the United States.
  • HEAT repeat sequences - A series of three to four amino acids repeated along the length of a protein; acronym HEAT comes from four proteins in which these repeated sequences have been found. The normal huntingtin protein contains 36 HEAT-like repeats, which fold up into a spiral structure and may serve as docking sites for other proteins. Also referred to as HEAT domains.
  • heat shock - stress upon the cell resulting from temperatures outside its tolerable range. Overheating the cell usually causes proteins to misfold because of the harsh environment, and will trigger the heat shock response.
  • heat shock factor 1 (HSF-1) - A protein that performs various cellular activities while associated with heat shock protein 90 (Hsp 90). HSF-1 initiates the production of heat shock proteins 40 and 70 when disassociated from Hsp 90.
  • heat shock protein (Hsp) - Proteins that are synthesized in organisms in response to various environmental stressors (such as extremes in temperature). There are various kinds of heat shock proteins, each of them performing different functions.
  • heat shock response - A mechanism cells use to maintain stability when subjected to stress. Heat shock response often involves the production of heat shock proteins.
  • helicase - An enzyme that unwinds the double helix of DNA to allow for replication.
  • heme - A compound made mostly of iron.
  • heme oxygenase - An enzyme that breaks down heme and plays various roles in the processes of oxidative stress and inflammation.
  • hemisphere - Half of the cerebral cortex (the brain has a left and right hemisphere).
  • hemoglobin - A substance found within red blood cells that binds to oxygen and carries it from the lungs to the tissues.
  • hemorrhage - A copious discharge of blood from the blood vessels.
  • hereditary - Something that is passed on through generations genetically. The inheritance of a hereditary disease is dependent upon the genes received from one’s parents.
  • heredity - The passing of traits from one generation to the next.
  • high-density lipoprotein (HDL) cholesterol - A complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood. High levels are associated with a decreased risk of atherosclerosis and coronary heart disease.
  • high pressure liquid chromatography (HPLC) - A piece of equipment used in labs to facilitate the separation of molecules under high pressure in a stainless steel column filled with a special chemical substance called a matrix.
  • high throughput machines - A system which enables researchers can rapidly and efficiently search through chemical compound libraries, each with thousands of different samples, testing each of them for positive interactions with the biological target
  • highly unsaturated fatty acids - Fatty acids that contain more than one double bond. These double bonds affect the chemical characteristics of the fatty acids, making them less solid and more fluid.
  • HIP-1 - huntingtin-interacting protein-1. It is a membrane-associated protein that interacts with the cytoskeleton. Huntingtin proteins with an expanded number of glutamines show decreased binding to HIP-1.
  • hippocampal - Of or relating to the hippocampus.
  • hippocampal region - Relating to the hippocampus, a complex structure involved with certain types of memory functions.
  • hippocampus - A part of the brain that plays a role in the establishment of new memories.
  • histones - Proteins that play a part in the regulation of gene transcription by helping to condense DNA into its compact form as chromosomes.
  • histone acetyltransferases - These enzymes add an acetyl group to histones, thus releasing the restricted access to DNA imposed by histones. Transcription factors can then bind to the DNA, allowing gene transcription to occur. Patients with HD tend to have decreased histone acetyltransferase activity.
  • histone deacetylase (HDAC) - These enzymes remove an acetyl group from histones, which allows histones to bind DNA and inhibit gene transcription.
  • histone deacetylase inhibitors (HDAC inhibitors) - Histone deacetylase inhibitors block the activity of histone deacetylases (HDACs). This leads to an increase in the overall level of transcriptional activity. This is thought to be therapeutic in a patient with HD because HDAC inhibitors help to combat the effects of HD by allowing essential genes to be transcribed, thus decreasing the rate of nerve cell death.
  • histone methyltransferase (HMT) - This enzyme adds a methyl group to histones, causing the DNA to coil up into chromosomes and preventing further transcription.
  • homeostatic - Of or relating to homeostasis.
  • homeostasis - A state of balance in the body maintained by several complex biological mechanisms that operate to offset disruptive changes.
  • homing - A process in which transplanted cells are attracted to and travel to an injured site.
  • homocysteine - A sulfur containing amino acid. Considered a risk factor for cardiovascular disease and possibly neurodegeneration.
  • homolog(ue) - 1. One member of a chromosome pair. 2. A gene similar in structure and evolutionary origin to a gene in another species.
  • homologous - Homologous chromosomes have corresponding DNA sequences and come from separate parents.
  • homologous chromosomes - A pair of chromosomes made up of two homologs. Homologous chromosomes have corresponding DNA sequences and come from separate parents; one homolog comes from the mother and the other comes from the father. Homologous chromosomes line up during meiosis.
  • homozygote - An individual with two identical alleles of a specific gene; matching genes at the same location on both homologous chromosomes.
  • hormone - A substance produced and released by certain parts of the body that can travel through the bloodstream and exert significant effects on other parts of the body (such as growth or changes in metabolism) over extended periods of time.
  • HPA axis - The hypothalamic-pituitary-adrenal axis (HPA axis) is a major part of the neuroendocrine system that controls reactions to stress. Species from humans to the most ancient organisms share components of the HPA axis. It is the mechanism for a set of interactions among glands, hormones and parts of the mid-brain that mediate a stress reaction.
  • HSF-1 - Abbreviation for heat shock factor 1.
  • Hsp - Abbreviation for heat shock protein.
  • Hsp 40 - The mouse analog of HDJ1.
  • HSP 70 and HSP 40 - Heat shock proteins that bind and associate with the misfolded huntingtin protein and prevent its aggregation. Production of Hsp 70 and Hsp 40 is stimulated by free HSF-1.
  • HSP 90 - A heat-shock protein that acts as a molecular chaperone to proteins involved in the progression of cancer. It also binds and associates with HSF-1. Geldenamycin binds to and inhibits Hsp 90, leading to both the misfolding of cancer-associated proteins and the freeing-up of HSF-1, which can then prevent misfolded huntingtin protein aggregation through the effects of Hsp 70 and Hsp 40.
  • Htt - Abbreviation sometimes used by researchers for the altered huntingtin protein.
  • human development - Continuous changes that occur during an individual’s life, starting at fertilization.
  • huntingtin aggregates - Rigid clumps of protein that form when a cell produces the altered form of huntingtin that causes HD. Huntingtin aggregates can also “kidnap” other proteins, and nerve cells with build-ups of huntingtin aggregates often die.
  • huntingtin protein - A key protein in Huntington’s disease. It exists in all humans but has a chemically different form in people with HD. Please note that although "Huntington's disease" is spelled with an "o", the correct spelling of the protein involved is "huntingtin" with an "i."
  • Huntington Study Group - "A non-profit group of physicians and other health care providers from medical centers in the U.S., Canada, Europe and Australia, experienced in the care of Huntington patients and dedicated to clinical research of Huntington's disease."
  • http://huntington-study-group.org/] - http://huntington-study-group.org/]
  • Huntington's disease - A hereditary neurological disorder characterized by movement, cognitive, and psychiatric symptoms.
  • Huntington’s Disease Society of America - A national health organization dedicated to finding a cure for Huntington’s Disease and to providing support for everyone affected with HD.
  • Huntington gene - The section of DNA that codes for the huntingtin protein. The scientific literature on HD refers to the gene as both the "Huntington gene" and the "huntingtin gene." For the purposes of this website, we will refer to the gene as the "Huntington gene" or, when it is in the altered form that results in HD, the "HD allele."
  • hydrocortisone - A drug that has much more mineralocorticoid activity than common glucocorticoid drugs and is therefore not suitable for long-term use. Hydocortisone is used extensively as a cream or lotion to treat skin irritations such as rashes or itches.
  • hydrogen bond - A weak bond between hydrogen and another atom (usually oxygen, fluorine, or nitrogen). Hydrogen bonds are critical in the formation of many biological molecules, including DNA and proteins.
  • hydrogen peroxide - A waste product of the cell that is a dangerous free radical.
  • hydrogenation - A process that alters the chemical structure of unsaturated fat and makes it more solid and long-lasting.
  • hydrolysis - Hydrolysis is the process by which a molecule is split in two by the addition of a water molecule, which has the chemical formula H2O. One of the parts gets an OH from the water molecule and the other part gets an H from the water.
  • hydrophilic - A property meaning “water loving,” describing molecules that are attracted to water.
  • hydrophobic - A property meaning "water fearing," describing molecules that are repelled by water.
  • hydroxyl radical - A free radical.
  • hyperglycemia - High glucose levels in the blood.
  • hypertension - High blood pressure.
  • hypothalamus - Small structure at the base of the brain that regulates many body functions, including appetite and body temperature.
  • hypothesis - A tentative explanation for an observation, phenomenon, or scientific problem that can be tested by further investigation.
  • hypoxia - Oxygen starvation at the cellular level.