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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 American Association for the Advancement of Science , 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 Hospital , Peter Bent Brigham Children's Hospital and Beth Israel Deaconess Medical Center, Beth Israel Hospital in Boston. In 1975, he held the position of ...
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New York City
New York, often called New York City (NYC), is the most populous city in the United States, located at the southern tip of New York State on one of the world's largest natural harbors. The city comprises five boroughs, each coextensive with a respective county. The city is the geographical and demographic center of both the Northeast megalopolis and the New York metropolitan area, the largest metropolitan area in the United States by both population and urban area. New York is a global center of finance and commerce, culture, technology, entertainment and media, academics, and scientific output, the arts and fashion, and, as home to the headquarters of the United Nations, international diplomacy. With an estimated population in 2024 of 8,478,072 distributed over , the city is the most densely populated major city in the United States. New York City has more than double the population of Los Angeles, the nation's second-most populous city.
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Brigham And Women's Hospital
Brigham and Women's Hospital (BWH or The Brigham) is a teaching hospital of Harvard Medical School and the largest hospital in the 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. Giles Boland, MD, serves as the hospital's current president. Brigham and Women's Hospital conducts the second largest hospital-based research program in the world, with an annual research budget of more than $630 million. History File:Bwh-longwood.jpg, 221 Longwood Avenue, formerly the Boston Lying-In Hospital building, part of Brigham and Women's Hospital but separate from the main building at 15–75 Francis Street; view from Longwood Avenue File:Free Hospital for Women.jpg, Former site of the Free Hospital for Women across the street from Olmsted Park. This institution was absorbed into Brigham and Women's Hospital. File:Brigham Circle at d ...
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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, 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 protein folding, 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 signaling, 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 e ...
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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 ...
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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 length ...
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Beta-amyloid
Amyloid beta (Aβ, Abeta or beta-amyloid) 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-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Both neurons and oligodendrocytes produce and release Aβ in the brain, contributing to formation of amyloid plaques. 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 mi ...
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Senile Plaque
Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia is a life-limiting condition, having a significant effect on the individual, their caregivers, and their social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process. Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, the most ...
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Tau Protein
The tau proteins (abbreviated from tubulin associated unit) form 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 m ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalent as the disease progresses. The motor symptoms are collectively called parkinsonism and include tremors, bradykinesia, spasticity, rigidity as well as postural instability (i.e., difficulty maintaining balance). Non-motor symptoms develop later in the disease and include behavior change (individual), behavioral changes or mental disorder, neuropsychiatric problems such as sleep abnormalities, psychosis, anosmia, and mood swings. Most Parkinson's disease cases are idiopathic disease, idiopathic, though contributing factors have been identified. Pathophysiology involves progressive nerve cell death, degeneration of nerve cells in the substantia nigra, a midbrain region that provides dopamine to the basal ganglia, a system invo ...
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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 wholly owned 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 ...
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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 and one of the founding members of Beth Israel Lahey Health. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916 by the Jewish community) and New England Deaconess Hospital (founded in 1896 by Methodist deaconesses). Among independent teaching hospitals, Beth Israel Deaconess Medical Center has ranked 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-Fa ...
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