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CA77.1
CA77.1 (CA) is a synthetic compound that activates chaperone-mediated autophagy (CMA) by increasing the expression of the lysosomal receptor for this pathway, LAMP2A, in lysosomes. CA77.1 is a derivative of earlier compound AR7, which shows potent CMA activation ''in vitro'' but is not suitable for ''in vivo'' use. CA77.1 is able to activate CMA ''in vivo'', and demonstrates brain penetrance and favorable pharmacokinetics. It has been shown in animal studies that ''in vivo'' administration of CA77.1 to enhance chaperone-mediated autophagy, may help to degrade toxic pathogenic protein products such as tau proteins and has potential applications in the treatment of Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me .... References {{pharm-stub Chloroar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
LAMP2
Lysosome-associated membrane protein 2 (LAMP2), also known as CD107b (Cluster of Differentiation 107b) and Mac-3, is a human gene. Its protein, LAMP2, is one of the lysosome-associated membrane glycoproteins. The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of the gene produces three variants - LAMP-2A, LAMP-2B and LAMP-2C. LAMP-2A is the receptor for chaperone-mediated autophagy. Recently it has been determined that antibodies against LAMP-2 account for a fraction of patients who get a serious kidney disease termed focal necrotizing glomerulonephritis. LAMP-2B is associated with Danon disease. Structure and tissue distribution The gene for LAMP2 has 9 coding exons and 2 alternate last exons, 9a and 9b. When the last exon is s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chaperone-mediated Autophagy
Chaperone-mediated autophagy (CMA) refers to the chaperone-dependent selection of soluble cytosolic proteins that are then targeted to lysosomes and directly translocated across the lysosome membrane for degradation. The unique features of this type of autophagy are the selectivity on the proteins that are degraded by this pathway and the direct shuttling of these proteins across the lysosomal membrane without the requirement for the formation of additional vesicles (Figure 1). Molecular components and steps The proteins that are degraded through CMA are cytosolic proteins or proteins from other compartments once they reach the cytosol. Therefore, some of the components that participate in CMA are present in the cytosol while others are located at the lysosomal membrane (Table I). Specific selection of proteins for degradation in all forms of autophagy came to further understanding as studies discovered the role of chaperones like hsc70. Although hsc70 targets cytosolic protein to ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lysosome
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane proteins, and its lumenal proteins. The lumen's pH (~4.5–5.0) is optimal for the enzymes involved in hydrolysis, analogous to the activity of the stomach. Besides degradation of polymers, the lysosome is involved in various cell processes, including secretion, plasma membrane repair, apoptosis, cell signaling, and energy metabolism. Lysosomes act as the waste disposal system of the cell by digesting used materials in the cytoplasm, from both inside and outside the cell. Material from outside the cell is taken up through endocytosis, while material from the inside of the cell is digested through autophagy. The sizes of the organelles vary greatly—the larger ones can be more than 10 times the size of the smaller ones. They we ... [...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] |
Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, 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 typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chloroarenes
In organic chemistry, an aryl halide (also known as haloarene) is an aromatic compound in which one or more hydrogen atoms, directly bonded to an aromatic ring are replaced by a halide. The haloarene are different from haloalkanes because they exhibit many differences in methods of preparation and properties. The most important members are the aryl chlorides, but the class of compounds is so broad that there are many derivatives and applications. Preparation The two main preparatory routes to aryl halides are direct halogenation and via diazonium salts. Direct halogenation In the Friedel-Crafts halogenation, Lewis acids serve as catalysts. Many metal chlorides are used, examples include iron(III) chloride or aluminium chloride. The most important aryl halide, chlorobenzene is produced by this route. Monochlorination of benzene is always accompanied by formation of the dichlorobenzene derivatives. Arenes with electron donating groups react with halogens even in the absence ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Quinoxalines
A quinoxaline, also called a benzopyrazine, in organic chemistry, is a heterocyclic compound containing a ring complex made up of a benzene ring and a pyrazine ring. It is isomeric with other naphthyridines including quinazoline, phthalazine and cinnoline. It is a colorless oil that melts just above room temperature. Although quinoxaline itself is mainly of academic interest, quinoxaline derivatives are used as dyes, pharmaceuticals (such as varenicline), and antibiotics such as olaquindox, carbadox, echinomycin, levomycin and actinoleutin. Synthesis They can be formed by condensing ''ortho''- diamines with 1,2-diketones. The parent substance of the group, quinoxaline, results when glyoxal is condensed with 1,2-diaminobenzene. Substituted derivatives arise when α-ketonic acids, α-chlorketones, α-aldehyde alcohols and α-ketone alcohols are used in place of diketones. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetamides
Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound ''N'',''N''-dimethylacetamide (DMA) is more widely used, but it is not prepared from acetamide. Acetamide can be considered an intermediate between acetone, which has two methyl (CH3) groups either side of the carbonyl (CO), and urea which has two amide (NH2) groups in those locations. Acetamide is also a naturally occurring mineral with the IMA symbol: Ace. Production Laboratory scale Acetamide can be produced in the laboratory from ammonium acetate by dehydration: : H4CH3CO2] → CH3C(O)NH2 + H2O Alternatively acetamide can be obtained in excellent yield via ammonolysis of acetylacetone under conditions commonly used in reductive amination. It can also be made from anhydrous acetic acid, acetonitrile and very well dried hydrogen chloride gas, usin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
