Dysregulation of the disintegrin-metalloproteinase ADAM10 may contribute to the development of diseases including tumorigenesis and Alzheimer's disease.
Acitretin, an aromatic retinoid, was found to exert an anti-amyloidogenic effect in mouse models for AD as well as in human patients by stimulating the alpha-secretase ADAM10.
These finding suggested that the 12-week treadmill exercise program reduced Aβ deposition in the hippocampus of APP/PS1 mice, possibly by regulating ADAM10 and BACE1 levels and by decreasing cholesterol-mediated lipid raft formation, indicating that exercise represents a therapeutic intervention to treat AD.
Among the proteolytic ADAMs, ADAM10 is the best characterized one due to its substrates Notch and amyloid precursor protein, where cleavage is required for nervous system development or linked to Alzheimer's disease (AD), respectively.
MiR-138 inhibited the expression of ADAM10 [a disintegrin and metalloproteinase domain-containing protein 10], promoted amyloid beta (Aβ) production, and induced synaptic and learning/memory deficits in APP/PS1 mice, while its suppression alleviated the AD-like phenotype in these mice.
These results indicate that by promoting the shedding of PrP<sup>C</sup> in human neurons, ADAM10 activation prevents the binding and cytotoxicity of AβO, revealing a potential therapeutic benefit of ADAM10 activation in AD.
The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls.
We tested whether downregulation of ADAM10 activity by its secreted endogenous inhibitor secreted-frizzled-related protein 1 (SFRP1) is a common trait of sporadic AD.
BACE1 mRNA level in AD subjects was significantly higher than those of healthy controls, whereas ADAM10 level was significantly lower in the AD subjects.
Thus, this investigation unravels mechanisms underlying ADAM10 downregulation by miR-140-5p and suggests that dysfunctional regulation of ADAM10 expression is exacerbated by AD-related neurotoxic effects.
As for Alzheimer's disease (AD) related pathology, chia seed not only increased α-secretase such as ADAM10 and insulin degrading enzyme (IDE), but also increased β-secretase including beta-secretase 1 (BACE1) and cathepsin B, with an overall effects of elevation in the hippocampal Aβ<sub>42</sub> level; chia seed slightly reduced p-Tauser404 in the hippocampus; while an elevation in neuro-inflammation with the activation of glial fibrillary acidic protein (GFAP) and Ibα-1 were observed post chia seed supplementation.
On microglia, increased ADAM10 cleavage of a rare variant of the scavenger receptor triggering receptor expressed on myeloid cells 2 may increase susceptibility to Alzheimer's disease.
The present study indicated that the rs653765 polymorphism might be associated with the risk and development of LOAD; in particular, the risk genotype, CC, may decrease the expression of ADAM10, influencing the plasma levels of sRAGE, and thus may be correlated with the clinical progression of AD.
Crucially, we also show that the Alzheimer's disease-associated H157Y TREM2 variant was shed more rapidly than wild type from HEK293 cells, possibly by a novel, batimastat- and ADAM10-siRNA-independent, sheddase activity.