Potential for New Peptide Drugs
That Easily Cross the Blood-Brain Barrier
A research team at Pusan National University has identified the atomic-level structure of a complex that inhibits the aggregation of amyloid beta (Aβ) proteins, which are known as the main cause of Alzheimer’s disease, and has proposed a next-generation dementia treatment candidate based on these findings.
On August 12, Pusan National University (President Choi Jaewon) announced that a research team led by Professor Jang Sebok from the Department of Molecular Biology had analyzed the binding structure of amyloid beta and transthyretin (TTR) using cryo-electron microscopy (Cryo-EM).
(From left) Professor Jang Sebok, Senior Researcher Lee Hanna. Courtesy of Pusan National University
Based on this information, the team designed a low-molecular-weight peptide that can easily cross the blood-brain barrier and confirmed its neuroprotective effects in cell experiments.
In the experiments, when both Aβ and the peptide were administered to a neuroblastoma cell line, cell viability increased, while reactive oxygen species (ROS) levels decreased and ATP was suppressed. The team explained that this approach could overcome the side effects and delivery limitations of existing antibody-based therapies, such as brain edema and hemorrhage.
Professor Jang Sebok stated, “By structurally elucidating the amyloid beta aggregation-inhibiting complex and presenting a precisely designed peptide candidate, we have laid the groundwork to overcome the limitations of current therapies. We expect this to contribute to structure-based drug development as it progresses through preclinical and clinical stages.”
This research was published online in the July 31 edition of the international journal Biochemical Pharmacology.
The study was supported by the Basic Research Program of the Ministry of Science and ICT, the Ministry of Education, and the National Research Foundation of Korea.
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