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Amyloid-β
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 back as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Beta-secretase 1
Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the ''BACE1'' gene. Expression of BACE1 is observed mainly in neurons. BACE1 is an aspartic acid protease important in the formation of myelin sheaths in peripheral nerve cells: in mice the expression of BACE1 is high in the postnatal stages, when myelination occurs. * The transmembrane protein contains two active site aspartate residues in its extracellular protein domain and may function as a dimer, its cytoplasmic tail is required for the correct maturation and an efficient intracellular trafficking, but doesn't affect the activity. It is produced as a pro-enzyme, the endoproteolitc removal occurs after BACE leaves Endoplasmic reticulum, in the Golgi apparatus. In addition the pro-peptide receives additional sugars to increase ... [...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 len ... [...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 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 than 2 ... [...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 the amyloid beta (Aβ) protein 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. 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 ultrastructure, ultrastructural component of neurofibrillary tangles. 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...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 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. Signs and symptoms CAA is associated with brain hemorrhages, particularly microhemorrhages. Since CAA can be caused by the same amyloid protein that is associated with Alzheimer's dementia, brain bleeds are more common in people who have a diagnosis of Alzheimer's disease. However, they can also occur in those who have no history of dementia. The bleeding within the brain is usually confined to a particular lobe and this is slightly different compared to brain bleeds which occur as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Brain
The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special senses such as vision, hearing and olfaction. Being the most specialized organ, it is responsible for receiving information from the sensory nervous system, processing those information (thought, cognition, and intelligence) and the coordination of motor control (muscle activity and endocrine system). While invertebrate brains arise from paired segmental ganglia (each of which is only responsible for the respective body segment) of the ventral nerve cord, vertebrate brains develop axially from the midline dorsal nerve cord as a vesicular enlargement at the rostral end of the neural tube, with centralized control over all body segments. All vertebrate brains can be embryonically divided into three parts: the forebrain (prosencep ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerebral Blood Vessel
Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Arteries deliver oxygenated blood, glucose and other nutrients to the brain. Veins carry "used or spent" blood back to the heart, to remove carbon dioxide, lactic acid, and other metabolic products. Because the brain would quickly suffer damage from any stoppage in blood supply, the cerebral circulatory system has safeguards including autoregulation of the blood vessels. The failure of these safeguards may result in a stroke. The volume of blood in circulation is called the cerebral blood flow. Sudden intense accelerations change the gravitational forces perceived by bodies and can severely impair cerebral circulation and normal functions to the point of becoming serious life-threatening conditions. The following description is based on ideal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ion Channel Hypothesis Of Alzheimer's Disease
The ion channel hypothesis of Alzheimer’s disease (AD), also known as the channel hypothesis or the amyloid beta ion channel hypothesis, is a more recent variant of the amyloid hypothesis of AD, which identifies amyloid beta (Aβ) as the underlying cause of neurotoxicity seen in AD. While the traditional formulation of the amyloid hypothesis pinpoints insoluble, fibrillar aggregates of Aβ as the basis of disruption of calcium ion homeostasis and subsequent apoptosis in AD, the ion channel hypothesis in 1993 introduced the possibility of an ion-channel-forming oligomer of soluble, non-fibrillar Aβ as the cytotoxic species allowing unregulated calcium influx into neurons in AD. The ion channel hypothesis is broadly supported as an explanation for the calcium ion influx that disrupts calcium ion homeostasis and induces apoptosis in neurons. Because the extracellular deposition of Aβ fibrils in senile plaques is not sufficient to predict risk or onset of AD, and clinical trials o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyloid
Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (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 in amyloid plaques around cells which can 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 are iatrogenic as they result from medical treatment. Prions are an infectious form of amyloids that can act as a template ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Folding
Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproducible process, a polypeptide folds into its characteristic three-dimensional structure from a random coil. Each protein exists first as an unfolded polypeptide or random coil after being translated from a sequence of mRNA to a linear chain of amino acids. At this stage the polypeptide lacks any stable (long-lasting) three-dimensional structure (the left hand side of the first figure). As the polypeptide chain is being synthesized by a ribosome, the linear chain begins to fold into its three-dimensional structure. Folding of many proteins begins even during translation of the polypeptide chain. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (the right hand side of the figure ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
