NYUAD researchers have developed small proteins called cell-penetrating peptides (CPPs) that prevent the aggregation of the Ab protein.
A team of researchers, led by NYU Abu Dhabi Assistant Professor of Biology Mazin Magzoub, has developed small proteins called cell-penetrating peptides (CPPs) that prevent the aggregation of the amyloid-b (Ab) protein associated with Alzheimer’s disease.
There is a growing interest in the use of proteins to develop treatments because they are biocompatible, biodegradable, and can selectively bind to specific targets, which reduces the potential for toxicity. Other pharmaceutically-desirable properties of proteins include greater chemical diversity than other biological molecule classes, and ease and low cost of production. However, a significant obstacle to the successful application of most proteins as therapeutics is their poor delivery to target organs and cells.
In a new study, the Magzoub lab in collaboration with Professor and NYU President Andrew Hamilton’s lab at NYU New York and Professor Astrid Gräslund’s lab at Stockholm University, report that they have engineered CPPs that effectively prevent the aggregation of Ab. CPPs are a special class of proteins that have the ability to reach all organs, including the brain, and to efficiently enter cells within these organs. Thus, the designed CPPs combine the attractive properties of proteins with potent therapeutic effects and highly efficient delivery to target cells.
A broad range of neurodegenerative diseases, including Huntington’s, Parkinson’s, and Alzheimer’s, are caused by the misfolding of disease-specific proteins. Once misfolded, these proteins build up in a process that damages neurons. Previously, the team showed that a naturally-derived CPP was able to protect against abnormal and harmful forms of the protein associated with prion diseases, a class of neurodegenerative disorders that include mad cow disease in cattle and Creutzfeldt-Jakob disease (CJD) in humans. Here, Magzoub and his collaborators extended this approach and specifically applied it to Alzheimer’s disease-causing Ab malformation.
In the paper titled Designed cell-penetrating peptide inhibitors of amyloid-beta aggregation and cytotoxicity, the researchers present the process of designing the Ab inhibitor CPPs. Using a range of techniques, they then extensively characterized the interactions of the designed CPPs with Ab. Specifically, they used established aggregation and cell viability assays to determine the effects of the designed CPPs on the aggregation and associated neurotoxicity of Ab. Simultaneously, they probed the cellular uptake and intracellular distribution of Ab in the presence of the CPPs with confocal fluorescence microscopy. Finally, they used a combination of experiments and computer simulations to shed light on the mechanism of binding of the CPPs to Ab. The results show that the designed CPPs stabilize the Ab protein in a non-aggregated, non-abnormal state, and inhibit Ab induced neurotoxicity.
The CPPs designed in this study effectively target Ab outside and inside neurons, thereby protecting them against the damage caused by Ab aggregation. “The designed CPPs represent a novel potential treatment strategy for Alzheimer’s disease,” said Magzoub. “These findings also reveal a general underlying principle for inhibition of pathogenic protein aggregation that will facilitate the design of even more potent CPP-based therapeutics for various neurodegenerative diseases.”
NYU Abu Dhabi is the first comprehensive liberal arts and science campus in the Middle East to be operated abroad by a major American research university. NYU Abu Dhabi has integrated a highly-selective liberal arts, engineering and science curriculum with a world center for advanced research and scholarship enabling its students to succeed in an increasingly interdependent world and advance cooperation and progress on humanity’s shared challenges. NYU Abu Dhabi’s high-achieving students have come from 115 nations and speak over 115 languages. Together, NYU’s campuses in New York, Abu Dhabi, and Shanghai form the backbone of a unique global university, giving faculty and students opportunities to experience varied learning environments and immersion in other cultures at one or more of the numerous study-abroad sites NYU maintains on six continents.
A metal railing can be seen giving way under the weight of the pushing and shoving students, with several plummeting to the concrete floor below at the El Alto university near La Paz.
The University is named after His Highness Sheikh Mohamed Bin Zayed Al Nahyan, who has long advocated for the UAE’s development of human capital through knowledge and scientific thinking to take the nation into the future.
The statement by UK Culture Secretary Oliver Dowden says he wants university students to be able to go home for Christmas comes as a soothing salve to address the woes of countless students in the country caught in lockdown.
This month’s series of sessions will honour those who perhaps have recently been unable to be with their children and read stories to them, due to being occupied by their duties on the frontlines and serving the country in its fight against the Covid-19 pandemic.
Sheikh Sultan Bin Ahmed Bin Sultan Al Qasimi, Deputy Ruler of Sharjah and President of the University of Sharjah (UoS), met on Monday morning the members of the Deans of the Faculties Council and the Directors of Research Centres and Institutes at the University’s main building.
Narratives of the Place (Sard Al Makan), an immersive and experiential theatrical show, which chronicles the history of Sharjah and its extraordinary journey and accomplishments over the past 50 years, will debut today (Tuesday, January 25) at 9:00 pm at Al Majaz Amphitheatre in Sharjah.
Schools in the UAE resumed in-person learning on Monday, after two weeks of using an online learning system as a precautionary measure, coinciding with the International Day of Education, which falls on Jan.24.