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- W1992138808 abstract "Abnormal elevation of amyloid β-peptide (Aβ) levels in the brain is the primary trigger for neuronal cell death specific to Alzheimer’s disease (AD). It is now evident that Aβ levels in the brain are manipulable due to a dynamic equilibrium between its production from the amyloid precursor protein (APP) and removal by amyloid clearance proteins. Clearance can be either enzymic or non-enzymic (binding/transport proteins). Intriguingly several of the main amyloid-degrading enzymes (ADEs) are members of the M13 peptidase family (neprilysin (NEP), NEP2 and the endothelin converting enzymes (ECE-1 and -2). A distinct metallopeptidase, insulin-degrading enzyme (IDE), also contributes to Aβ degradation in the brain. The ADE family currently embraces more than 20 members, both membrane-bound and soluble, and of differing cellular locations. NEP plays an important role in brain function terminating neuropeptide signals. Its decrease in specific brain areas with age or after hypoxia, ischaemia or stroke contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP (and other genes) by the APP intracellular domain (AICD) and its dependence on the cell type and APP isoform expression suggest possibilities for selective manipulation of NEP gene expression in neuronal cells. We have also observed that another amyloid-clearing protein, namely transthyretin (TTR), is also regulated in the neuronal cell by a mechanism similar to NEP. Dependence of amyloid clearance proteins on histone deacetylases and the ability of HDAC inhibitors to up-regulate their expression in the brain opens new avenues for developing preventive strategies in AD." @default.
- W1992138808 created "2016-06-24" @default.
- W1992138808 creator A5042857386 @default.
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- W1992138808 date "2014-09-17" @default.
- W1992138808 modified "2023-10-15" @default.
- W1992138808 title "Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease" @default.
- W1992138808 cites W1502785574 @default.
- W1992138808 cites W1507990444 @default.
- W1992138808 cites W1519404743 @default.
- W1992138808 cites W1521975614 @default.
- W1992138808 cites W1538944936 @default.
- W1992138808 cites W1543111690 @default.
- W1992138808 cites W1551466091 @default.
- W1992138808 cites W1576709629 @default.
- W1992138808 cites W1577922439 @default.
- W1992138808 cites W1588345803 @default.
- W1992138808 cites W1596429639 @default.
- W1992138808 cites W1596950278 @default.
- W1992138808 cites W1660631781 @default.
- W1992138808 cites W1683102335 @default.
- W1992138808 cites W1700257669 @default.
- W1992138808 cites W1709714829 @default.
- W1992138808 cites W1722833357 @default.
- W1992138808 cites W1800849354 @default.
- W1992138808 cites W1803624194 @default.
- W1992138808 cites W1890520376 @default.
- W1992138808 cites W1901339959 @default.
- W1992138808 cites W1916136752 @default.
- W1992138808 cites W1966225158 @default.
- W1992138808 cites W1966734666 @default.
- W1992138808 cites W1966900192 @default.
- W1992138808 cites W1967408430 @default.
- W1992138808 cites W1967740861 @default.
- W1992138808 cites W1967794260 @default.
- W1992138808 cites W1971039109 @default.
- W1992138808 cites W1971381167 @default.
- W1992138808 cites W1971729688 @default.
- W1992138808 cites W1971855284 @default.
- W1992138808 cites W1973415774 @default.
- W1992138808 cites W1973779722 @default.
- W1992138808 cites W1974749844 @default.
- W1992138808 cites W1975046995 @default.
- W1992138808 cites W1975088357 @default.
- W1992138808 cites W1979127284 @default.
- W1992138808 cites W1981021670 @default.
- W1992138808 cites W1983199625 @default.
- W1992138808 cites W1983839663 @default.
- W1992138808 cites W1987341100 @default.
- W1992138808 cites W1988986946 @default.
- W1992138808 cites W1992907194 @default.
- W1992138808 cites W1993553556 @default.
- W1992138808 cites W1994210129 @default.
- W1992138808 cites W1995234894 @default.
- W1992138808 cites W1996087645 @default.
- W1992138808 cites W1997397907 @default.
- W1992138808 cites W1997609831 @default.
- W1992138808 cites W1998730409 @default.
- W1992138808 cites W1999061258 @default.
- W1992138808 cites W1999728316 @default.
- W1992138808 cites W2002001290 @default.
- W1992138808 cites W2002207246 @default.
- W1992138808 cites W2004186568 @default.
- W1992138808 cites W2004984841 @default.
- W1992138808 cites W2005481412 @default.
- W1992138808 cites W2006092729 @default.
- W1992138808 cites W2008580181 @default.
- W1992138808 cites W2010101046 @default.
- W1992138808 cites W2010474330 @default.
- W1992138808 cites W2010890708 @default.
- W1992138808 cites W2012657344 @default.
- W1992138808 cites W2016808139 @default.
- W1992138808 cites W2017197594 @default.
- W1992138808 cites W2018317955 @default.
- W1992138808 cites W2020355217 @default.
- W1992138808 cites W2027619670 @default.
- W1992138808 cites W2028305875 @default.
- W1992138808 cites W2028403300 @default.
- W1992138808 cites W2029427029 @default.
- W1992138808 cites W2029752828 @default.
- W1992138808 cites W2030011352 @default.
- W1992138808 cites W2031157188 @default.
- W1992138808 cites W2032501367 @default.
- W1992138808 cites W2033016640 @default.
- W1992138808 cites W2033499475 @default.
- W1992138808 cites W2035892094 @default.
- W1992138808 cites W2036785198 @default.
- W1992138808 cites W2037024442 @default.
- W1992138808 cites W2038663652 @default.
- W1992138808 cites W2039481158 @default.
- W1992138808 cites W2041892165 @default.
- W1992138808 cites W2043062604 @default.
- W1992138808 cites W2044166038 @default.
- W1992138808 cites W2044611006 @default.
- W1992138808 cites W2044827730 @default.
- W1992138808 cites W2048361834 @default.
- W1992138808 cites W2048526645 @default.
- W1992138808 cites W2052092391 @default.