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. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia, depression, apathy, and impulsivity at times. The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age, and can start at any age but are usually seen around the age of 40. The disease may develop earlier in each successive generation. About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinson's disease rather than those of chorea.
Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to around 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system.Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.
Samuel Weiss is a Canadian neurobiologist.
Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes. They are typically identified in the human by co-expression of PDGFRA and CSPG4.
The rostral migratory stream (RMS) is a specialized migratory route found in the brain of some animals along which neuronal precursors that originated in the subventricular zone (SVZ) of the brain migrate to reach the main olfactory bulb (OB). The importance of the RMS lies in its ability to refine and even change an animal's sensitivity to smells, which explains its importance and larger size in the rodent brain as compared to the human brain, as our olfactory sense is not as developed. This pathway has been studied in the rodent, rabbit, and both the squirrel monkey and rhesus monkey. When the neurons reach the OB they differentiate into GABAergic interneurons as they are integrated into either the granule cell layer or periglomerular layer.
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.
Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
Huntingtin-associated protein 1 (HAP1) is a protein which in humans is encoded by the HAP1 gene. This protein was found to bind to the mutant huntingtin protein (mHtt) in proportion to the number of glutamines present in the glutamine repeat region.
Quinolinic acid, also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. It is a colorless solid. It is the biosynthetic precursor to niacin.
Pridopidine is an orally administrated small molecule investigational drug. Pridopidine is a selective and potent Sigma-1 Receptor agonist. It is being developed by Prilenia Therapeutics and is currently in late-stage clinical development for Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS).
Anne Buckingham Young is an American physician and neuroscientist who has made major contributions to the study of neurodegenerative diseases, with a focus on movement disorders like Huntington's disease and Parkinson's disease. Young completed her undergraduate studies at Vassar College and earned a dual MD/PhD from Johns Hopkins Medical School. She has held faculty positions at University of Michigan and Harvard University. She became the first female chief of service at Massachusetts General Hospital when she was appointed Chief of Neurology in 1991. She retired from this role and from clinical service in 2012. She is a member of many academic societies and has won numerous awards. Young is also the only person to have been president of both the international Society for Neuroscience and the American Neurological Association.
Jeffrey Bryan Carroll is an American scientific researcher in the field of Huntington's disease (HD). As a carrier of the abnormal gene that causes HD, he is also a public advocate for families affected by the disease, and co-founder of the HD research news platform HDBuzz. His life and work were the subject of a 2011 Gemini award-nominated CBC documentary feature. Carroll is an Associate Professor of neuroscience in the Department of Psychology at Western Washington University.
Epigenetic regulation of neurogenesis is the role that epigenetics plays in the regulation of neurogenesis.
Cajal–Retzius cells are a heterogeneous population of morphologically and molecularly distinct reelin-producing cell types in the marginal zone/layer I of the developmental cerebral cortex and in the immature hippocampus of different species and at different times during embryogenesis and postnatal life.
Extrasynaptic NMDA receptors are glutamate-gated neurotransmitter receptors that are localized to non-synaptic sites on the neuronal cell surface. In contrast to synaptic NMDA receptors that promote acquired neuroprotection and synaptic plasticity, extrasynaptic NMDA receptors are coupled to activation of death-signaling pathways. Extrasynaptic NMDA receptors are responsible for initiating excitotoxicity and have been implicated in the etiology of neurodegenerative diseases, including stroke, Huntington’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS).
Cagla Eroglu is a Turkish neuroscientist and associate professor of cell biology and neurobiology at Duke University in Durham, North Carolina and an investigator with the Howard Hughes Medical Institute. Eroglu is also the director of graduate studies in cell and molecular biology at Duke University Medical Center. Eroglu is a leader in the field of glial biology, and her lab focuses on exploring the role of glial cells, specifically astrocytes, in synaptic development and connectivity.
Hu Hailan is a Chinese neuroscientist, professor, and executive director of the Center for Neuroscience at Zhejiang University School of Medicine in Hangzhou, China. Hu explores neural mechanisms underlying social behaviors and psychiatric diseases. She specifically explores the neural substrates of social rank and the role of neuron-glia interactions in driving depressive behaviors. Hu discovered the anatomical and molecular targets of ketamine's fast-acting antidepressant effects to be localized to the lateral habenular circuits in rodents. Hu was also the first scientist outside of Europe and America to be awarded the IBRO-Kemali Prize in over 20 years. She is also a member of the Jiusan Society.
Alexei Verkhratsky, sometimes spelled Alexej, is a professor of neurophysiology at the University of Manchester best known for his research on the physiology and pathophysiology of neuroglia, calcium signalling, and brain ageing. He is an elected member and vice-president of Academia Europaea, of the German National Academy of Sciences Leopoldina, of the Real Academia Nacional de Farmacia (Spain), of the Slovenian Academy of Sciences and Arts, of Polish Academy of Sciences, and Dana Alliance for Brain Initiatives, among others. Since 2010, he is a Ikerbasque Research Professor and from 2012 he is deputy director of the Achucarro Basque Center for Neuroscience in Bilbao. He is a distinguished professor at Jinan University, China Medical University of Shenyang, and Chengdu University of Traditional Chinese Medicine and is an editor-in-chief of Cell Calcium, receiving editor for Cell Death and Disease, and Acta Physiologica and member of editorial board of many academic journals.
The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the requisite nutrients to activated neurons. The NVU addresses the brain's unique dilemma of having high energy demands yet low energy storage capacity. In order to function properly, the brain must receive substrates for energy metabolism–mainly glucose–in specific areas, quantities, and times. Neurons do not have the same ability as, for example, muscle cells, which can use up their energy reserves and refill them later; therefore, cerebral metabolism must be driven in the moment. The neurovascular unit facilitates this ad hoc delivery and, thus, ensures that neuronal activity can continue seamlessly.
