Targeting amyloid precursor protein shuttling and processing - long before amyloid beta formation. Publique Deposited
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MLA citation style. 3720. https://mushare.marian.edu/concern/generic_works/20b58198-5801-4522-aac5-a602afc8ed82?locale=fr Targeting Amyloid Precursor Protein Shuttling and Processing - Long Before Amyloid Beta Formation.
APA citation style(3720). Targeting amyloid precursor protein shuttling and processing - long before amyloid beta formation. https://mushare.marian.edu/concern/generic_works/20b58198-5801-4522-aac5-a602afc8ed82?locale=fr
Chicago citation styleTargeting Amyloid Precursor Protein Shuttling and Processing - Long before Amyloid Beta Formation. 3720. https://mushare.marian.edu/concern/generic_works/20b58198-5801-4522-aac5-a602afc8ed82?locale=fr
Note: These citations are programmatically generated and may be incomplete.
<strong>Targeting early steps in amyloid-beta production:</strong> Alzheimer's disease (AD) has a long history as the “amyloid deposit” disorder. Many disorders are now known to be caused by protein ?-sheet misfolding and aggregation (<em>e.g</em>., Parkinson's disease: ?-synuclein; Huntington's disease: Huntingtin; spongiform encephalopathy: prion protein) (Rambaran and Serpell, 2008). Commonly, the family of amyloid mental disorders often have multiple aggregating proteins with most having one or two highlighted. For example in AD, amyloid beta (A?) extracellular aggregates in senile plaques (SP) are the most obvious postmortem observation along with intracellular tau tangles. However, AD patients often have accumulation of TDP43 and ?-synuclein (in Lewy bodies) (Josephs <em>et al.</em>, 2014). While reducing A? remains the main AD target, there has been a recent shift from targeting the late forming amyloid plaques, to earlier steps in production of A?. Recent work has suggested that small oligomers of A? could be the neurotoxic compounds with structures on the order of A? octomers forming pores in neuronal membranes causing cell death (Arbor <em>et al.</em>, 2016). Under this paradigm, the larger extracellular amyloid plaques could actually be neuroprotective <em>via</em> a mechanism of sequestering the more deleterious A? monomers. In addition to not being neurotoxic (wrong marker physically) the amyloid plaques present late in disease after neuronal death has occurred (wrong marker temporally). While the field continues to target the already existing A? in AD patients, the effort to target even the production of A? has been reinvigorated. Possible targets include the initial production of amyloid precursor protein (APP), APP insertion in membrane lipid rafts, APP shuttling to early endosome compartments, and processing of APP. The molecular pathways causing this shift away from targeting amyloid plaques as well as therapeutics will be the content of this perspective.