期刊
EBIOMEDICINE
卷 78, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2022.103952
关键词
Prader-Wlli syndrome; Gender specific genomic imprinting; Hyperphagia; Foetal nutritional pathways
资金
- PWS
Prader-Willi syndrome is a genetic disorder characterized by abnormal brain development and placental nutritional pathways, leading to symptoms such as hyperphagia. Understanding the underlying genetic and physiological mechanisms could lead to new interventions for this syndrome.
Prader-Willi syndrome arises as a consequence of absent paternal copies of maternally imprinted genes at 15q11-13. Such gender-of-origin imprinted genes are expressed in the brain and also in mammalian placenta where paternally expressed imprinted genes drive foetal nutritional demand. We hypothesise that the PWS phenotype is the result of the genotype impacting two pathways: first, directly on brain development and secondly, on placental nutritional pathways that results in its down-regulation and relative foetal starvation. The early PWS phenotype establishes the basis for the later characteristic phenotype. Hyperphagia. and other phenotypic characteristics arise as a conse-quence of impaired hypothalamic development. Hypothalamic feeding pathways become set in a state indicative of starvation, with a high satiety threshold and a dysfunctional neurophysiological state due to incorrect representations of reward needs, based on inputs that indicate a false requirement for food. Our hypotheses, if confirmed, would lead to novel and effective interventions. Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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