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Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease
Kang Seong Su,Ahn Eun Hee,Ye Keqiang 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with age as a major risk factor. AD is the most common dementia with abnormal structures, including extracellular senile plaques and intraneuronal neurofibrillary tangles, as key neuropathologic hallmarks. The early feature of AD pathology is degeneration of the locus coeruleus (LC), which is the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The spread of Tau deposits is first initiated in the LC and is transported in a stepwise manner from the entorhinal cortex to the hippocampus and then to associative regions of the neocortex as the disease progresses. Most recently, we reported that the NE metabolite DOPEGAL activates delta-secretase (AEP, asparagine endopeptidase) and triggers pathological Tau aggregation in the LC, providing molecular insight into why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in the disease and how δ-secretase mediates the spread of Tau pathology to the rest of the brain. This review summarizes our current understanding of the crucial role of δ-secretase in driving and spreading AD pathologies by cleaving multiple critical players, including APP and Tau, supporting that blockade of δ-secretase may provide an innovative disease-modifying therapeutic strategy for treating AD.
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Yuxin Li,Keqiang Su,Peikang Bai,Liyun Wu,Bin Liu,Hongwen Su,Wenbo Du 대한금속·재료학회 2019 METALS AND MATERIALS International Vol.25 No.5
The Ti/TiBCN composite coatings were fabricated on the substrate of Ti6Al4V alloy by laser cladding. The effects of TiBCNcontent on the microstructre, microhardness, corrosion resistance and tribological properties of the composite coatings werestudied. The results showed that, when the TiBCN content was 60 wt%, the composite coatings were mainly composed ofthe dendritic and rod-shaped TiBCN phases, small white lump TiC phases, fine lamellar TiN phases, small and scatteredwhite block TiB2phases, In addition, there was a small quantity of short whisker Al3Tiphases and uniform layer blockTiAl phases. Furhtermore, the maximum microhardness was 1596 HV, which was about 4.6 folds greater than that of thesubstrate; the corrosion potential (Ecorr) reached − 1.258 V and the corrosion current density (Icorr) was 4.035 × 10−5 A/cm2,which was one order lower than that of the substrate (1.172 × 10−4 A/cm2); the worn surface was relatively smooth and themass loss (1.22 g) was only 9/50 of that of the substrate (6.71 g).
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