New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction

• Published in: International journal of molecular sciences 2022-02, Vol.23 (3), p.1829
• Main Authors: Tsuneura, Yumi, Nakai, Tsuyoshi, Mizoguchi, Hiroyuki, Yamada, Kiyofumi
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animal models; Animals; Brain; Extracellular matrix; Gene expression; Gene Expression Regulation, Developmental; Glutamic acid receptors; Humans; Kinases; Learning; Matrix protein; Mental disorders; Mental Disorders - drug therapy; Mental Disorders - metabolism; Mice; Molecular Targeted Therapy; Morphology; N-Methyl-D-aspartic acid receptors; Phosphorylation; Proteins; Psychotropic drugs; Reelin protein; Reelin Protein - genetics; Reelin Protein - metabolism; Review; Schizophrenia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031829

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 -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.