Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Debomoy K. Lahiri¹  Deborah K. Sokol² 

[1] 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;Section of Pediatrics, Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States;

关键词: ASD;    microcephaly;    amyloid precursor protein;    T21;    Down’s syndrome;    Alzheimer’s disease;   

DOI  :  10.3389/fnmol.2023.1201723

 received in 2023-04-07, accepted in 2023-08-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

Recent studies promote new interest in the intersectionality between autism spectrum disorder (ASD) and Alzheimer’s Disease. We have reported high levels of Amyloid-β Precursor Protein (APP) and secreted APP-alpha (sAPPa) and low levels of amyloid-beta (Aβ) peptides 1–40 and 1–42 (Aβ40, Aβ42) in plasma and brain tissue from children with ASD. A higher incidence of microcephaly (head circumference less than the 3rd percentile) associates with ASD compared to head size in individuals with typical development. The role of Aβ peptides as contributors to acquired microcephaly in ASD is proposed. Aβ may lead to microcephaly via disruption of neurogenesis, elongation of the G1/S cell cycle, and arrested cell cycle promoting apoptosis. As the APP gene exists on Chromosome 21, excess Aβ peptides occur in Trisomy 21-T21 (Down’s Syndrome). Microcephaly and some forms of ASD associate with T21, and therefore potential mechanisms underlying these associations will be examined in this review. Aβ peptides’ role in other neurodevelopmental disorders that feature ASD and acquired microcephaly are reviewed, including dup 15q11.2-q13, Angelman and Rett syndrome.

【 授权许可】

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Copyright © 2023 Sokol and Lahiri.