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N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-β(1-16) peptides as arginine specific endopeptidase potentially enhancing risk of Alzheimer’s diseaseстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 12 февраля 2018 г.
- Авторы: Kugaevskaya Elena V., Veselovsky Alexander V., Indeykina Maria I., Solovyeva Nina I., Zharkova Maria S., Popov Igor A., Nikolaev Eugene N., Mantsyzov Alexey B., Makarov Alexander A., Kozin Sergey A.
- Журнал: Scientific reports
- Том: 8
- Год издания: 2018
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 298
- DOI: 10.1038/s41598-017-18567-5
- Аннотация: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Amyloid-β (Aβ) aggregation is likely to be the major cause of AD. In contrast to humans and other mammals, that share the same Aβ sequence, rats and mice are invulnerable to AD-like neurodegenerative pathologies, and Aβ of these rodents (ratAβ) has three amino acid substitutions in the metalbinding domain 1-16 (MBD). Angiotensin-converting enzyme (ACE) cleaves Aβ-derived peptide substrates, however, there are contradictions concerning the localization of the cleavage sites within Aβ and the roles of each of the two ACE catalytically active domains in the hydrolysis. In the current study by using mass spectrometry and molecular modelling we have tested a set of peptides corresponding to MBDs of Aβ and ratAβ to get insights on the interactions between ACE and these Aβ species. It has been shown that the N-domain of ACE (N-ACE) acts as an arginine specific endopeptidase on the Aβ and ratAβ MBDs with C-amidated termini, thus assuming that full-length Aβ and ratAβ can be hydrolyzed by N-ACE in the same endopeptidase mode. Taken together with the recent data on the molecular mechanism of zincdependent oligomerization of Aβ, our results suggest a modulating role of N-ACE in AD pathogenesis.
- Добавил в систему: Манцызов Алексей Борисович