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Microtubule-associated Proteins
In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtubules of the cellular cytoskeleton. MAPs are integral to the stability of the cell and its internal structures and the transport of components within the cell. Function MAPs bind to the tubulin subunits that make up microtubules to regulate their stability. A large variety of MAPs have been identified in many different cell types, and they have been found to carry out a wide range of functions. These include both stabilizing and destabilizing microtubules, guiding microtubules towards specific cellular locations, cross-linking microtubules and mediating the interactions of microtubules with other proteins in the cell. Within the cell, MAPs bind directly to the tubulin dimers of microtubules. This binding can occur with either polymerized or depolymerized tubulin, and in most cases leads to the stabilization of microtubule structure, further encouraging polymerization. Usually, it is ...
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Neuropathology Case IX 05
Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole-body autopsies. Neuropathologists usually work in a department of anatomic pathology Anatomical pathology (''Commonwealth'') or anatomic pathology (''U.S.'') is a medical specialty that is concerned with the diagnosis of disease based on the macroscopic, microscopic, biochemical, immunologic and molecular examination ..., but work closely with the clinical disciplines of neurology, and neurosurgery, which often depend on neuropathology for a diagnosis. Neuropathology also relates to forensic pathology because brain disease or brain injury can be related to cause of death. Neuropathology should not be confused with neuropathy, which refers to disorders of the nerves themselves (usually in the peripheral nervous system) rather than the tissues. In neuropathology, the branches of the specializations of nervous system as well as the tissues co ...
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Dendrite
A dendrite (from Ancient Greek language, Greek δένδρον ''déndron'', "tree") or dendron is a branched cytoplasmic process that extends from a nerve cell that propagates the neurotransmission, electrochemical stimulation received from other neural cells to the cell body, or soma (biology), soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons (usually via their axons) via synapses which are located at various points throughout the dendritic tree. Dendrites play a critical role in integrating these synaptic inputs and in determining the extent to which action potentials are produced by the neuron. Structure and function Dendrites are one of two types of cytoplasmic processes that extrude from the cell body of a neuron, the other type being an axon. Axons can be distinguished from dendrites by several features including shape, length, and function. Dendrites often taper off in shape and are shorter, ...
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MAP4
Microtubule-associated protein 4 is a protein that in humans is encoded by the ''MAP4'' gene. The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2 Microtubule-associated protein 2 is a protein in humans that is encoded by the ''MAP2'' gene. Function This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family were originally isolated ...) and microtubule-associated protein tau ( MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 ( CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple alternatively spli ...
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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 ...
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Paclitaxel
Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered by intravenous injection. There is also an albumin-bound formulation. Common side effects include hair loss, bone marrow suppression, numbness, allergic reactions, muscle pains, and diarrhea. Other side effects include heart problems, increased risk of infection, and lung inflammation. There are concerns that use during pregnancy may cause birth defects. Paclitaxel is in the taxane family of medications. It works by interference with the normal function of microtubules during cell division. Paclitaxel was isolated in 1971 from the Pacific yew and approved for medical use in 1993. It is on the World Health Organization's List of Essential Medicines. It has been made from precursors, and through cell culture. Medical use Paclitaxel ...
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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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N-terminal End
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the carboxylic acid, carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the C-terminus, and a free amine group on the other end called the N-terminus. By convention, peptide sequences are written N-terminus to C-terminus, left to right (in Writing system#Directionality, LTR writing systems). This correlates the translation (biology), translation direction to the text direction, because when a protein is translated from messenger RNA, it is created from the N-terminus to the C-terminus, as amino acids are added to the carboxyl end of the protein. Chemistry Each amino acid has an amine group and a carboxylic group. Amino acids link to one anot ...
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Structural Domain
In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or Disulfide bond, disulfide bridges. Domains often form functional units, such as the calcium-binding EF-hand, EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimera (protein), chimeric ...
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C-terminal End
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Chemistry Each amino acid has a carboxyl group and an amine group. Amino acids link to one another to form a chain by a dehydration reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an unbound amine group, the N-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus. Function C-terminal retention signals While the N-terminus of a ...
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Conservation (genetics)
In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids (DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( xenologous sequences). Conservation indicates that a sequence has been maintained by natural selection. A highly conserved sequence is one that has remained relatively unchanged far back up the phylogenetic tree, and hence far back in geological time. Examples of highly conserved sequences include the RNA components of ribosomes present in all domains of life, the homeobox sequences widespread amongst eukaryotes, and the tmRNA in bacteria. The study of sequence conservation overlaps with the fields of genomics, proteomics, evolutionary biology, phylogenetics, bioinformatics and mathematics. History The discovery of the role of DNA in heredity, and observations by Frederick Sanger of variation between animal insulins in 1949, promp ...
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MAPT
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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MAP2
Microtubule-associated protein 2 is a protein in humans that is encoded by the ''MAP2'' gene. Function This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family were originally isolated since they copurify with tubulin in polymerization experiments: tubulin in cell extracts can be made to polymerize to produce microtubules (MT) under the influence of heat and the addition of Guanosine triphosphate, GTP, and the MT can then be collected by centrifugation. When this is done a series of microtubule associated proteins are collected along with the MT and can be detected by SDS-PAGE and other methods. Brain extracts are rich in several of these proteins, MAP2 being one of these. The single MAP2 gene produces four major transcripts producing four proteins, MAP2A, MAP2B, MAP2C and MAP2D. MAP2A and MAP2B are very high molecular weight proteins, with apparent molecular weight on SDS-PAGE about 250 kDa, while MAP2C and MAP2D ar ...
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