APPlications of amyloid-β precursor protein metabolites in macrocephaly and autism spectrum disorder

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Deborah K. Sokol¹  Debomoy K. Lahiri² 

[1] Department of Neurology, Section of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States;Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States;Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States;Indiana Alzheimer Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, United States;

关键词: ASD;    macrocephaly;    amyloid precursor protein;    adamalysins;    brain development;    overgrowth;   

DOI  :  10.3389/fnmol.2023.1201744

 received in 2023-04-07, accepted in 2023-07-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

Metabolites of the Amyloid-β precursor protein (APP) proteolysis may underlie brain overgrowth in Autism Spectrum Disorder (ASD). We have found elevated APP metabolites (total APP, secreted (s) APPα, and α-secretase adamalysins in the plasma and brain tissue of children with ASD). In this review, we highlight several lines of evidence supporting APP metabolites’ potential contribution to macrocephaly in ASD. First, APP appears early in corticogenesis, placing APP in a prime position to accelerate growth in neurons and glia. APP metabolites are upregulated in neuroinflammation, another potential contributor to excessive brain growth in ASD. APP metabolites appear to directly affect translational signaling pathways, which have been linked to single gene forms of syndromic ASD (Fragile X Syndrome, PTEN, Tuberous Sclerosis Complex). Finally, APP metabolites, and microRNA, which regulates APP expression, may contribute to ASD brain overgrowth, particularly increased white matter, through ERK receptor activation on the PI3K/Akt/mTOR/Rho GTPase pathway, favoring myelination.

【 授权许可】

Unknown   
Copyright © 2023 Sokol and Lahiri.