Version 1
: Received: 12 February 2024 / Approved: 14 February 2024 / Online: 14 February 2024 (09:26:18 CET)
How to cite:
Chang, H.; Wang, I. Unraveling the Complex Pathology of Neurodegenerative Diseases: Multiple Prions, Cross-β Networks and Baicalein's ReproFold. Preprints2024, 2024020790. https://doi.org/10.20944/preprints202402.0790.v1
Chang, H.; Wang, I. Unraveling the Complex Pathology of Neurodegenerative Diseases: Multiple Prions, Cross-β Networks and Baicalein's ReproFold. Preprints 2024, 2024020790. https://doi.org/10.20944/preprints202402.0790.v1
Chang, H.; Wang, I. Unraveling the Complex Pathology of Neurodegenerative Diseases: Multiple Prions, Cross-β Networks and Baicalein's ReproFold. Preprints2024, 2024020790. https://doi.org/10.20944/preprints202402.0790.v1
APA Style
Chang, H., & Wang, I. (2024). Unraveling the Complex Pathology of Neurodegenerative Diseases: Multiple Prions, Cross-β Networks and Baicalein's ReproFold. Preprints. https://doi.org/10.20944/preprints202402.0790.v1
Chicago/Turabian Style
Chang, H. and I-Fan Wang. 2024 "Unraveling the Complex Pathology of Neurodegenerative Diseases: Multiple Prions, Cross-β Networks and Baicalein's ReproFold" Preprints. https://doi.org/10.20944/preprints202402.0790.v1
Abstract
The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
