scholarly journals Substrate interaction inhibits γ-secretase production of amyloid-β peptides

2020 ◽  
Vol 56 (17) ◽  
pp. 2578-2581
Author(s):  
Jing Zhao ◽  
Yuanyuan Xiao ◽  
Xinyue Liu ◽  
Soohyun Kim ◽  
Xianzhong Wu ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Precursor Proteins ◽  
Substrate Interaction ◽  
Precursor Proteins

A novel compound C1 interacts with C-terminal juxtamembrane lysines of amyloid precursor proteins and inhibits γ-secretase production of Aβ.

scholarly journals Proteolysis of Chimeric β-Amyloid Precursor Proteins Containing the Notch Transmembrane Domain Yields Amyloid β-like Peptides

2002 ◽  
Vol 277 (17) ◽  
pp. 15069-15075 ◽  
Author(s):  
Jimin Zhang ◽  
Wenjuan Ye ◽  
Rong Wang ◽  
Michael S. Wolfe ◽  
Barry D. Greenberg ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Amyloid Β ◽  
Amyloid Precursor Proteins ◽  
Precursor Proteins ◽  
Β Amyloid

scholarly journals Amyloidogenic Peptides in Human Neuro-Degenerative Diseases and in Microorganisms: A Sorrow Shared Is a Sorrow Halved?

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 925 ◽  
Author(s):  
Kristina Endres
Keyword(s):  
Neurodegenerative Diseases ◽  
Self Assembly ◽  
Amyloid Β ◽  
Degenerative Diseases ◽  
Human Beings ◽  
Precursor Proteins ◽  
Long Time ◽  
Health And Disease ◽  
Amyloidogenic Peptides ◽  
Toxic Peptides

The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that microbes also possess amyloidogenic peptides is intriguing. Transmission of amyloids by iatrogenic means or by consumption of contaminated meat from diseased animals is a well-known fact. What if also our microbial commensals might drive human amyloidosis or suffer from our aggregated amyloids? Moreover, as the microbial amyloids are evolutionarily older, we might learn from these organisms how to cope with the sword of Damocles forged of endogenous, potentially toxic peptides. This review summarizes knowledge about the interplay between human amyloids involved in neurodegenerative diseases and microbial amyloids.

scholarly journals Amyloid β-peptides interfere with mitochondrial preprotein import competence by a coaggregation process

2016 ◽  
Vol 27 (21) ◽  
pp. 3257-3272 ◽  
Author(s):  
Giovanna Cenini ◽  
Cornelia Rüb ◽  
Michael Bruderek ◽  
Wolfgang Voos
Keyword(s):  
Mitochondrial Protein ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Cellular Damage ◽  
Aβ Peptides ◽  
Mitochondrial Functions ◽  
Major Species ◽  
Protein Biogenesis ◽  
Precursor Proteins ◽  
Strong Inhibitory Effect

Aβ peptides play a central role in the etiology of Alzheimer disease (AD) by exerting cellular toxicity correlated with aggregate formation. Experimental evidence has shown intraneuronal accumulation of Aβ peptides and interference with mitochondrial functions. Nevertheless, the relevance of intracellular Aβ peptides in the pathophysiology of AD is controversial. Here we found that the two major species of Aβ peptides, in particular Aβ42, exhibited a strong inhibitory effect on the preprotein import reactions essential for mitochondrial biogenesis. However, Aβ peptides interacted only weakly with mitochondria and did not affect the inner membrane potential or the structure of the preprotein translocase complexes. Aβ peptides significantly decreased the import competence of mitochondrial precursor proteins via an extramitochondrial coaggregation mechanism. Coaggregation and import inhibition were significantly stronger for the longer peptide Aβ42, correlating with its importance in AD pathology. Our results demonstrate that direct interference of aggregation-prone Aβ peptides with mitochondrial protein biogenesis represents a crucial aspect of the pathobiochemical mechanisms contributing to cellular damage in AD.

Dimerization and Structural Stability of Amyloid Precursor Proteins Affected by the Membrane Microenvironments

2017 ◽  
Vol 57 (6) ◽  
pp. 1375-1387 ◽  
Author(s):  
Fude Sun ◽  
Long Chen ◽  
Peng Wei ◽  
Mengya Chai ◽  
Xiufang Ding ◽  
...  
Keyword(s):  
Structural Stability ◽  
Amyloid Precursor Proteins ◽  
Precursor Proteins
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