Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ijms23031829
Keywords
reelin; neuropsychiatric disorders; development; ADAMTS-3
Funding
- KAKENHI from Japan Society for the Promotion of Science [JP19K21811, JP19H03532, JP20H03428]
- Takeda Science Foundation
- Mishima Kaiun Memorial Foundation
- Hori Sciences and Arts Foundation
- biomedical research from SRF
- AMED from Japan Agency for Medical Research and Development [JP21wm0425007, JP21wm0425014]
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Reelin, an important protein for brain development and function, is found to be associated with neuropsychiatric disorders. Supplementing Reelin could improve learning and neuronal dysfunctions in animal models. Therefore, studying the role of Reelin in neuropsychiatric disorders and potential therapeutic approaches is of great significance.
Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin plays a crucial role in the regulation of N-methyl-D-aspartate receptor-dependent synaptic function, and its expression decreases postnatally. Clinical studies showed reductions in Reelin protein and mRNA expression levels in patients with psychiatric disorders; however, the causal relationship remains unclear. Reelin-deficient mice exhibit an abnormal neuronal morphology and behavior, while Reelin supplementation ameliorates learning deficits, synaptic dysfunctions, and spine loss in animal models with Reelin deficiency. These findings suggest that the neuronal deficits and brain dysfunctions associated with the down-regulated expression of Reelin are attenuated by enhancements in its expression and functions in the brain. In this review, we summarize findings on the role of Reelin in neuropsychiatric disorders and discuss potential therapeutic approaches for neuropsychiatric disorders associated with Reelin dysfunctions.
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