A ratiometric electrochemical strategy for sensitive determination of Furin activity based on dual signal amplification and antifouling nanosurfaces

The Analyst ◽  
2017 ◽  
Vol 142 (22) ◽  
pp. 4215-4220 ◽  
Author(s):  
Dazhi Yao ◽  
Wenqi Zhao ◽  
Limin Zhang ◽  
Yang Tian

Developing a sensitive and accurate method for Furin activity is still the bottleneck for understanding the role played by Furin in cell-surface systems and even in Alzheimer's disease.

2016 ◽  
Author(s):  
Sandra van der Velden ◽  
Christoph Moenninghoff ◽  
Isabel Wanke ◽  
Martha Jokisch ◽  
Christian Weimar ◽  
...  

2021 ◽  
Author(s):  
Swati Mishra ◽  
Allison Knupp ◽  
Marcell Szabo ◽  
Chizuru Kinoshita ◽  
Dale W. Hailey ◽  
...  

Background: Loss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer's disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD's cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1). Methods: We used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network. Finally, we analyzed alterations in gene expression in SORL1 depleted neurons using RNA-sequencing. Results: We find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1's role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling Conclusion: Collectively, and together with other recent observations, these findings suggest that SORL1 is a key and broad regulator of retromer-dependent endosomal recycling in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer's disease.


2016 ◽  
Vol 12 ◽  
pp. P442-P442
Author(s):  
Chongzhao Ran ◽  
Jing Yang ◽  
Steven H. Liang ◽  
Anna Moore

2017 ◽  
Vol 9 (32) ◽  
pp. 4740-4746 ◽  
Author(s):  
BinBin Wei ◽  
Mingyan Liu ◽  
Zaixing Chen ◽  
Minjie Wei

An efficient UPLC-MS/MS method for determining schisandrin in rat plasma and brain microdialysates has been developed and validated.


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