Much of Alzheimer’s research has pegged the accumulation of amyloid-beta (Aβ) proteins within the brain as a major component in neurodegeneration. While many researchers seek pharmaceutical solutions to the protein buildup, one group is exploring a very different solution: fighting proteins with proteins.
A team of researchers led by Dr. Mazin Magzoub, an assistant professor of biology at NYU Abu Dhabi, recently released a paper on the use of small proteins strands, called cell-penetrating peptides (CPPs), to prevent the accumulation of Aβ proteins within the brain. The paper, titled Designed cell-penetrating peptide inhibitors of amyloid-beta aggregation and cytotoxicity, was published in the journal Cell Reports Physical Science.
The therapeutic potential of proteins has been the focus of much research, due to their biocompatibility, biodegradability, and ability to bind to specific targets, all of which reduce the risk for toxicity. However, the use of proteins is hampered by the difficulty in delivering them to intended targets. However, CPPs, a special class of proteins made up of short chains of amino acids linked by peptide bonds, are used naturally by the body to transport materials through biological membranes, including the blood-brain barrier.
Many neurodegenerative diseases, including Alzheimer’s, are characterized by damage to neurons, the building blocks of the nervous system. Other diseases include Huntington’s and Parkinson’s. Dr. Magzoub and his team previously showed that lab-designed CPPs were capable of combatting proteins associated with prion diseases, which include mad cow disease and Creutzfeldt-Jakob disease. In their new study, Magzoub and his team sought to apply the same approach to Alzheimer’s disease and Aβ proteins.
Dr. Magzoub’s lab, in coordination with the labs of Dr. Andrew Hamilton, professor and president of NYU, and Dr. Astrid Gräslund, professor at Stockholm University, reported on the process for creating CPPs with anti-Aβ potential. Using a variety of techniques to analyze the process, their report sheds light on the mechanisms behind the binding of CPPs to Aβ proteins. Their results that the designed CPPs effectively targeted Aβ proteins both outside and inside the neurons, protecting them from damage caused by Aβ accumulation.
“The designed CPPs represent a novel potential treatment strategy for Alzheimer’s disease,” stated Dr. 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.”