Shin, Jisu Yang, Seung-Hoon Du, Young Eun Park, Keunwan Kim, DaWon Shin, Daniel Kim, Jungwoo Kim, Seong-Hwan Kim, Yun Kyung Shin, Jongheon Oh, Dong-Chan Kim, YoungSoo 2024-01-19T15:33:51Z 2024-01-19T15:33:51Z 2022-01-10 2021-01 2542-4823 https://pubs.kist.re.kr/handle/201004/117570 Background: Alzheimer's disease (AD) is characterized by the aggregation of two pathological proteins, amyloid-beta (A beta) and tau, leading to neuronal and cognitive dysfunction. Clearance of either A beta or tau aggregates by immunotherapy has become a potential therapy, as these aggregates are found in the brain ahead of the symptom onset. Given that A beta and tau independently and cooperatively play critical roles in AD development, AD treatments might require therapeutic approaches to eliminate both aggregates together. Objective: We aimed to discover a chemical drug candidate from natural sources for direct dissociation of both insoluble A beta and tau aggregates through in vitro assessments. Methods: We isolated four borrelidin chemicals from a saltern-derived halophilic actinomycete strain of rare genus Nocardiopsis and simulated their docking interactions with A beta fibrils. Then, anti-cytotoxic, anti-A beta, and anti-tau effects of borrelidins were examined by MTT assays with HT22 hippocampal cell line, thioflavin T assays, and gel electrophoresis. Results: When HT22 cells were exposed to A beta aggregates, the treatment of borrelidins alleviates the A beta-induced toxicity. These anti-cytotoxic effects can be derived from the inhibitory functions of borrelidins against the A beta aggregation as shown in thioflavin T and gel electrophoretic analyses. Among them, especially borrelidin, which exhibits the highest probability of docking, not only dissociates A beta aggregates but also directly regulates tau aggregation. Conclusion: Borrelidin dissociates insoluble A beta and tau aggregates together and our findings support the view that it is possible to develop an alternative chemical approach mimicking anti-A beta or anti-tau immunotherapy for clearance of both aggregates. English IOS PRESS Borrelidin from Saltern-Derived Halophilic Nocardiopsis sp. Dissociates Amyloid-beta and Tau Fibrils Article 10.3233/ADR-200247 1 JOURNAL OF ALZHEIMERS DISEASE REPORTS, v.5, no.1, pp.7 - 13 JOURNAL OF ALZHEIMERS DISEASE REPORTS 5 1 7 13 Y scopus 000651079100002 Neurosciences Neurosciences & Neurology Article IN-VITRO AGGREGATION ACCESS Alzheimer&apos s disease amyloid-beta borrelidin natural products tau