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Aβ
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 tha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyloid Plaque
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of amyloid beta (Aβ) protein that present 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. 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 than 200 μm2), which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid. History In 1892, Paul Blocq and Gheor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyloid Plaques
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of amyloid beta (Aβ) protein that present mainly in the grey matter of the brain. Degeneration (medical), 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 brain, aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. The plaques are highly variable in shape and size; in tissue sections immunohistochemistry, 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 than 200 μm2), which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Experimental Models Of Alzheimer's Disease
Experimental models of Alzheimer's disease are organism or cellular models used in research to investigate biological questions about Alzheimer's disease as well as develop and test novel therapeutic treatments. Alzheimer's disease is a progressive neurodegenerative disorder associated with aging, which occurs both sporadically (the most common form of diagnosis) or due to familial passed mutations in genes associated with Alzheimer's pathology. Common symptoms associated with Alzheimer's disease include: memory loss, confusion, and mood changes. As Alzheimer's disease affects around 55 million patients globally and accounts for approximately 60-70% of all dementia cases, billions of dollars are spent yearly towards research to better understand the biological mechanisms of the disease as well as develop effective therapeutic treatments for it. Researchers commonly use post-mortem human tissue or experimental models to conduct experiments relating to Alzheimer's disease. Experimenta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years. The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the di ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyloid-beta Precursor Protein
Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many 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 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 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 from 639 to 770 amino acids, with certain isoforms pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteinopathy
In medicine, proteinopathy ( 'pref''. protein -pathy 'suff''. disease proteinopathies ''pl''.; proteinopathic ''adj''), or proteopathy, protein conformational disorder, or protein misfolding disease, is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a toxic gain-of-function) or they can lose their normal function. The proteinopathies include such diseases as Creutzfeldt–Jakob disease (and a variant associated with mad cow disease) and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. The term ''proteopathy'' was first proposed in 2000 by Lary Walker and Harry LeVine. The concept of proteopathy can trace its origins to the mid-19th century, wh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyloid
Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions ( misfolding) and form fibrous deposits within and around cells. These protein misfolding and deposition processes disrupt the healthy function of tissues and organs. Such amyloids have been associated with (but not necessarily as the cause of) more than 50 human diseases, known as amyloidosis, and may play a role in some neurodegenerative diseases. Some of these diseases are mainly sporadic and only a few cases are familial. Others are only familial. Some result from medical treatment. Prions are an infectious form of amyloids that can act as a templa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerebral Amyloid Angiopathy
Cerebral amyloid angiopathy (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to medium blood vessels of the central nervous system and meninges. The term ''congophilic'' is sometimes used because the presence of the abnormal aggregations of amyloid can be demonstrated by microscopic examination of brain Biological tissue, tissue after staining with Congo red. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis. Types Several familial variants exist. The condition is usually associated with amyloid beta. However, there are types involving other amyloid peptides: * The "Hereditary cystatin C amyloid angiopathy, Icelandic type" is associated with cystatin C amyloid (ACys). * The "British type" and "Danish type" are associated with British amyloid (ABri) and Danish amyloid (ADan) respectively. Both peptides are linked to mutations in ITM2B. * Familial amyloidosis-Finnish type is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., (superoxide radical), OH ( hydroxyl radical) and (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer, Parkin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prion
A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), which are fatal and transmissible neurodegenerative diseases affecting both humans and animals. These proteins can misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein, leading to an abnormal Protein tertiary structure, three-dimensional structure that can propagate misfolding in other proteins. The term ''prion'' comes from "proteinaceous infectious particle". Unlike other infectious agents such as viruses, bacteria, and fungi, prions do not contain nucleic acids (DNA or RNA). Prions are mainly twisted Protein isoform, isoforms of the major prion protein (PrP), a naturally occurring protein with an uncertain function. They are the hypothesized cause of various transmissible spongiform encephalopath ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
