Dennis J. Selkoe
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Dennis J. Selkoe
Dennis J. Selkoe (born 25 September 1943) is an American physician (neurologist) known for his research into the molecular basis of Alzheimer's disease. In 1985 he became Co-Director of the Center for Neurological Diseases and from 1990, Vincent and Stella Coates Professor of Neurological Diseases at Harvard Medical School. He is also a Fellow of the AAAS and a member of the National Academy of Medicine. Career and early life Selkoe studied at Columbia University (Bachelor's degree 1965) and the University of Virginia School of Medicine (M. D. 1969). He took up a residency at the University of Pennsylvania Hospital (1969). From 1970 to 1972, he performed research at the National Institutes of Health and continued his residency as a neurologist at the Peter Bent Brigham Children's Hospital and Beth Israel Hospital in Boston. In 1975, he held the position of instructor at the Brigham and Women's Hospital in Boston, before moving up to assistant professor in 1978. In 1978, ...
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New York City
New York, often called New York City or NYC, is the List of United States cities by population, most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the List of United States cities by population density, most densely populated major city in the United States, and is more than twice as populous as second-place Los Angeles. New York City lies at the southern tip of New York (state), New York State, and constitutes the geographical and demographic center of both the Northeast megalopolis and the New York metropolitan area, the largest metropolitan area in the world by urban area, urban landmass. With over 20.1 million people in its metropolitan statistical area and 23.5 million in its combined statistical area as of 2020, New York is one of the world's most populous Megacity, megacities, and over 58 million people live within of the city. New York City is a global city, global Culture of New ...
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Brigham And Women's Hospital
Brigham and Women's Hospital (BWH) is the second largest teaching hospital of Harvard Medical School and the largest hospital in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Along with Massachusetts General Hospital, it is one of the two founding members of Mass General Brigham, the largest healthcare provider in Massachusetts. Sunil Eappen serves as the hospital's current president. Brigham and Women's Hospital conducts the second largest (behind MGH) hospital-based research program in the world, with an annual research budget of more than $630 million. Pioneering achievements at BWH have included the world's first successful heart valve operation and the world's first solid organ transplant. In the 2020 ''U.S. News & World Report'' hospital rankings, BWH was ranked second in Massachusetts (behind MGH) and twelfth nationally. History Brigham and Women's Hospital was established with the 1980 merger of three Harvard-affiliated hospita ...
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Élan
Elan Corporation plc was a major drugs firm based in Dublin, Ireland, which had major interests in the United States. It was listed on the New York Stock Exchange as ELN, the Irish Stock Exchange as ELN.I, and the London Stock Exchange as ELN.L. In 2013, the company merged with Perrigo to form Perrigo Company PLC. History The company was founded in Ireland by American businessman Don Panoz in 1969. In the late 1990s, its value on the Irish Stock Exchange reached over €20bn. However, in 2002, an accounting scandal and investor reactions to the global slump, caused a major devaluation resulting in a share price slump of over 90%. In July 2010, Élan was fined $203m for its marketing of epilepsy drugs. In February 2013, Elan decided to dispose of the rights to sell Tysabri to Biogen Idec for $3.25 billion. Products in development In neurology, Elan was focused on building upon its research and experience in the area of neuropathologies such as Alzheimer’s disease, whe ...
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Gamma-secretase
Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when cleaved by both gamma and beta secretase, produces a short 37-43 amino acid peptide called amyloid beta whose abnormally folded fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44. Subunits and assembly The gamma secretase complex consists of four individual proteins: PSEN1 (presenilin-1), nicastrin, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2). Recent eviden ...
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Presenilin
Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes, called '' PSEN1'' (located on chromosome 14 in humans) that codes for presenilin 1 (PS-1) and '' PSEN2'' (on chromosome 1 in humans) that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm ''C. elegans'' has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1. Presenilins undergo cleavage in an alpha helical region of one of the cytoplasmic loops to produce a large N-terminal and a smaller C-terminal fragment that together form part of the functional protein. Cleavage of presenilin 1 can be ...
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Amyloid Precursor Protein
Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity, and iron export. It is coded for by the gene ''APP'' and regulated by substrate presentation. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose Amyloid#Structure, amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Genetics Amyloid-beta precursor protein is an ancient and highly Conserved sequence, conserved protein. In humans, the gene ''APP'' is located on chromosome 21 and contains 18 exons spanning 290 kilobases. Several alternative splicing isoforms of APP have been observed in humans, ranging in len ...
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Beta-amyloid
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers (known as "seeds") can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold. A study has suggested that APP and its amyloid potential is of ancient origins, dating as far b ...
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Senile Plaque
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. Abnormal neurites in amyloid plaques are tortuous, often swollen axons and dendrites. The neurites contain a variety of organelles and cellular debris, and many of them include characteristic paired helical filaments, the ultrastructural component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve with an average plaque area of 400-450 square micrometers (µm²). The smallest plaques (less th ...
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Tau Protein
The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintaining the stability of microtubules in axons and are abundant in the neurons of the central nervous system (CNS), where the cerebral cortex has the highest abundance. They are less common elsewhere but are also expressed at very low levels in CNS astrocytes and oligodendrocytes. Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease are associated with tau proteins that have become hyperphosphorylated insoluble aggregates called neurofibrillary tangles. The tau proteins were identified in 1975 as heat-stable proteins essential for microtubule assembly, and since then they have been characterized as intrinsically disordered proteins. Function Microtubule stabilization Tau proteins are found mo ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor symptoms are also known as ...
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Business Wire
Business Wire is an American company that disseminates full-text press releases from thousands of companies and organizations worldwide to news media, financial markets, disclosure systems, investors, information web sites, databases, bloggers, social networks and other audiences. It is a subsidiary of Berkshire Hathaway. History Business Wire was founded in 1961 by Lorry I. Lokey. It started by sending releases to 16 media outlets in California. Business Wire launched its website in May 1995. In 2000, ahead of its main competitor PR Newswire, Business Wire ended the practice of distributing news to financial outlets 15 minutes before anyone else, to provide immediate, equal access to company information as noted by the SEC's fair disclosure regulation (Reg FD). Business Wire's first wholly owned European operation launched in 2001, with the opening of an office in London. On June 1, 2005, Business Wire entered the German Ad-Hoc market with a disclosure network for companies with ...
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Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a teaching hospital of Harvard Medical School. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and New England Deaconess Hospital (founded in 1896). Among independent teaching hospitals, Beth Israel Deaconess Medical Center consistently ranks in the top three recipients of biomedical research funding from the National Institutes of Health. Research funding totals nearly $200 million annually. BIDMC researchers run more than 850 active sponsored projects and 200 clinical trials. The Harvard-Thorndike General Clinical Research Center, the oldest clinical research laboratory in the United States, has been located on this site since 1973. Overview BIDMC is one of the largest hospitals in New England, is affiliated with Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center, the largest cancer institution in the country. The hospital is part of the ...
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