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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(10):2663-2666
Angiogenin (ANG) is a human ribonuclease that is compromised in patients with amyotrophic lateral sclerosis (ALS). ANG also promotes neovascularization, and can induce hemorrhage and encourage tumor growth. The causal neurodegeneration of ALS is associated with reactive oxygen species, which are also known to elicit the oxidative cleavage of carbon–boron bonds. We have developed a synthetic boronic acid mask that restrains the ribonucleolytic activity of ANG. The masked ANG does not stimulate endothelial cell proliferation but protects astrocytes from oxidative stress. By differentiating between the two dichotomous biological activities of ANG, this strategy could provide a viable pharmacological approach for the treatment of ALS. 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(41):12764-12767
Transactivation response element (TAR) DNA‐binding protein 43 (TDP‐43) misfolding is implicated in several neurodegenerative diseases characterized by aggregated protein inclusions. Misfolding is believed to be mediated by both the N‐ and C‐terminus of TDP‐43; however, the mechanistic basis of the contribution of individual domains in the process remained elusive. Here, using single‐molecule fluorescence and ensemble biophysical techniques, and a wide range of pH and temperature conditions, we show that TDP‐43NTD is thermodynamically stable, well‐folded and undergoes reversible oligomerization. We propose that, in full‐length TDP‐43, association between folded N‐terminal domains enhances the propensity of the intrinsically unfolded C‐terminal domains to drive pathological aggregation. 相似文献
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