Abstract
Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits, with a notably limited range of brain-targeted medications, particularly in the field of nanomedicine. Herein, we introduce the brain-targeted H2S donor cross-linked nanomicelle, named mannose-PEG600-lipoic acid (Man-LA). Man-LA demonstrates enhanced stability and precise brain delivery by interacting with glucose transporter 1 (GLUT1) in astrocytes, facilitating a gradual release of H2S that is modulated by glutathione (GSH). In vivo, studies suggest that Man-LA alleviates symptoms of ASD, correlating with increased expression of aerobic glycolysis enzymes, elevated lactate production, and higher H2S levels, while preventing damage to hippocampal neurons. In vitro, Man-LA tightly binds to aldehyde dehydrogenase family 3 member B1 (Aldh3b1) in astrocytes, upregulating its expression. This interaction promotes aerobic glycolysis and enhances lactate production. These findings suggest a connection between ASD deficits and the dysregulation of astrocytic aerobic glycolysis, underscoring the role of H2S. Identifying the Aldh3b1 gene within aerobic glycolysis pathways provides a promising target for ASD treatment.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.