Formation of a β‐Endorphin Corona Mitigates Alzheimer's Amyloidogenesis
Source abstract
Abstract
Abstract Senile plaques, comprised of nanosized aggregates of amyloid‐β (Aβ) peptides in the brain, are a pathological hallmark of Alzheimer's disease (AD). On the other hand, regular physical exercise is known to significantly reduce the risk of developing AD. Here, it is reported on the transformation and toxicity mitigation of Aβ amyloid aggregation by a spontaneous “corona” of β‐endorphin, a major peptide hormone released upon exercise to suppress post‐exercise pain. Given that both Aβ and β‐endorphin co‐localize extracellularly in the brain, it is postulated that β‐endorphin may mitigate the toxicity of Aβ aggregation via direct molecular interactions, thereby contributing to an exercise‐mediated reduction of AD risk. Combining biophysical characterizations in vitro with atomistic discrete molecular dynamics simulations in silico, a strong interaction is shown between β‐endorphin and Aβ, where β‐endorphins are located at the periphery to render a corona of their hetero‐complexes with Aβ. Cell viability, immunofluorescence and western blotting assays further revealed that the corona shielded cellular exposure to Aβ aggregates and suppressed the toxicity of Aβ in vivo. This work offered a new molecular mechanism for the benefits of physical exercise, which may facilitate a rational design of future therapy and prevention strategies against AD and dementia.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Alzheimer's disease research and treatments · Supramolecular Self-Assembly in Materials · Biochemical effects in animals
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Physical Science and Technology Ningbo University Ningbo 315211 China
Department of Physics and Astronomy Clemson University Clemson SC 29634 USA
Drug Delivery Disposition and Dynamics Monash Institute of Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia
Laboratory of Immunology and Nanomedicine & China‐Italy Joint Laboratory of Pharmacobiotechnology for Medical Immunomodulation Laboratory of Inflammation and Vaccines Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China
School of Biomedical Sciences and Engineering Guangzhou International Campus South China University of Technology Guangzhou 510006 China
Liver Cancer Institute Zhongshan Hospital Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education Fudan University Shanghai 200032 China
School of Medicine Ningbo University Ningbo 315211 China
Funding
National Key Research and Development Program of China · Ministry of Science and Technology of the People's Republic of China · Natural Science Foundation of Guangdong Province · Fundamental Research Funds for the Provincial Universities of Zhejiang · Natural Science Foundation of Ningbo Municipality · National Outstanding Youth Science Fund Project of National Natural Science Foundation of China · National Institute of General Medical Sciences
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