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https://doi.org/10.3390/brainsci10020122
Title: | Enhancing ?-secretase processing for Alzheimer’s disease—a view on SFRP1 | Authors: | Tang, B.L. | Keywords: | ADAM10 Alzheimer’s disease Amyloid ? (A?) Secreted-frizzled-related protein 1 (SFRP1) |
Issue Date: | 2020 | Publisher: | MDPI AG | Citation: | Tang, B.L. (2020). Enhancing ?-secretase processing for Alzheimer’s disease—a view on SFRP1. Brain Sciences 10 (2) : 122. ScholarBank@NUS Repository. https://doi.org/10.3390/brainsci10020122 | Rights: | Attribution 4.0 International | Abstract: | Amyloid ? (A?) peptides generated via sequential ?-and ?-secretase processing of the amyloid precursor protein (APP) are major etiopathological agents of Alzheimer’s disease (AD). However, an initial APP cleavage by an ?-secretase, such as the a disintegrin and metalloproteinase domain-containing protein ADAM10, precludes ?-secretase cleavage and leads to APP processing that does not produce A?. The latter appears to underlie the disease symptom-attenuating effects of a multitude of experimental therapeutics in AD animal models. Recent work has indicated that an endogenous inhibitor of ADAM10, secreted-frizzled-related protein 1 (SFRP1), is elevated in human AD brains and associated with amyloid plaques in mouse AD models. Importantly, genetic or functional attenuation of SFRP1 lowered A? accumulation and improved AD-related histopathological and neurological traits. Given SFRP1?s well-known activity in attenuating Wnt signaling, which is also commonly impaired in AD, SFRP1 appears to be a promising therapeutic target for AD. This idea, however, needs to be addressed with care because of cancer enhancement potentials resulting from a systemic loss of SFRP1 activity, as well as an upregulation of ADAM10 activity. In this focused review, I shall discuss ?-secretase-effected APP processing in AD with a focus on SFRP1, and explore the contrasting perspectives arising from the recent findings. © 2020 by the author. Licensee MDPI, Basel, Switzerland. | Source Title: | Brain Sciences | URI: | https://scholarbank.nus.edu.sg/handle/10635/196209 | ISSN: | 2076-3425 | DOI: | 10.3390/brainsci10020122 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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