IGF2 在记忆、神经发育障碍和神经退行性疾病中的作用。
IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases.
机构信息
Center for Neural Science, New York University, New York, NY 10003, USA.
出版信息
Trends Neurosci. 2023 Jun;46(6):488-502. doi: 10.1016/j.tins.2023.03.007. Epub 2023 Apr 6.
Abstract
Insulin-like growth factor 2 (IGF2) emerged as a critical mechanism of synaptic plasticity and learning and memory. Deficits in IGF2 in the brain, serum, or cerebrospinal fluid (CSF) are associated with brain diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Increasing IGF2 levels enhances memory in healthy animals and reverses numerous symptoms in laboratory models of aging, neurodevelopmental disorders, and neurodegenerative diseases. These effects occur via the IGF2 receptor (IGF2R) - a receptor that is highly expressed in neurons and regulates protein trafficking, synthesis, and degradation. Here, I summarize the current knowledge regarding IGF2 expression and functions in the brain, particularly in memory, and propose a novel conceptual model for IGF2/IGF2R mechanisms of action in brain health and diseases.
摘要
胰岛素样生长因子 2（IGF2）是突触可塑性和学习记忆的关键机制。大脑、血清或脑脊液（CSF）中 IGF2 的缺陷与包括阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和肌萎缩侧索硬化症（ALS）在内的脑部疾病有关。增加 IGF2 水平可增强健康动物的记忆力，并逆转衰老、神经发育障碍和神经退行性疾病的实验室模型中的许多症状。这些作用是通过 IGF2 受体（IGF2R）发生的，IGF2R 在神经元中高度表达，调节蛋白质运输、合成和降解。在这里，我总结了目前关于 IGF2 在大脑中（特别是在记忆中）的表达和功能的知识，并提出了一个关于 IGF2/IGF2R 在大脑健康和疾病中的作用机制的新的概念模型。
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本文引用的文献
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: Development, Genetic and Epigenetic Abnormalities.
Cells. 2022 Jun 10;11(12):1886. doi: 10.3390/cells11121886.
2
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Nat Neurosci. 2022 Jun;25(6):688-701. doi: 10.1038/s41593-022-01084-8. Epub 2022 Jun 2.
3
Insulin-like growth factor 2 and autophagy gene expression alteration arise as potential biomarkers in Parkinson's disease.
Sci Rep. 2022 Feb 7;12(1):2038. doi: 10.1038/s41598-022-05941-1.
4
Insulin-like Growth Factor II Prevents MPP+ and Glucocorticoid Mitochondrial-Oxidative and Neuronal Damage in Dopaminergic Neurons.
Antioxidants (Basel). 2021 Dec 24;11(1):41. doi: 10.3390/antiox11010041.
5
Endosomal Recycling Defects and Neurodevelopmental Disorders.
Cells. 2022 Jan 3;11(1):148. doi: 10.3390/cells11010148.
6
The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth.
Dev Cell. 2022 Jan 10;57(1):63-79.e8. doi: 10.1016/j.devcel.2021.12.005. Epub 2021 Dec 27.
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Neurotrauma Rep. 2021 Oct 20;2(1):453-460. doi: 10.1089/neur.2021.0031. eCollection 2021.
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9
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Redox Biol. 2021 Oct;46:102095. doi: 10.1016/j.redox.2021.102095. Epub 2021 Aug 8.
10
Linking transport and translation of mRNAs with endosomes and mitochondria.
EMBO Rep. 2021 Oct 5;22(10):e52445. doi: 10.15252/embr.202152445. Epub 2021 Aug 17.
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