RELN and Associated Diseases

Creative Biolabs has been a long-term expert in the field of drug discovery. Based on our years of experience and advanced platforms, we can provide technical support services at all stages of your projects. Here we describe the RELN gene and associated diseases for our clients.

Introduction of Reelin

Encoded by the RELN gene, reelin is a serine protease that plays an important role in regulating neuronal migration during cerebral cortex development. Composed of 3461 amino acids, the relative molecular mass of reelin is 388 kDa. There is a short C-terminal region in the final reelin domain that is necessary for reelin secretion. Reelin is found mainly in the brain and in small amounts in other tissues and organs, such as the liver, thyroid, adrenal gland, and fallopian tubes. Reelin can bind to its cell surface receptors very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) and ultimately lead to phosphorylation of the intracellular protein disabled-1 (Dab1) and downstream signaling cascades activation.

Functions of Reelin

Reelin exhibits multiple functional roles depending on the timing of expression and localization. During the development period, reelin plays an important role in the early development of the brain. Reelin controls the direction of radial glial cell growth and ensures the correct positioning of neurons in the spinal cord, while increased reelin expression alters the morphology of migrating neurons. In the adult nervous system, reelin regulates the continuous migration of neuroblasts. In addition, reelin stimulates the development of dendrites and dendritic spines.

Schematic representation of the RELN signaling pathways in dendritic spines. Fig.1 Schematic representation of the RELN signaling pathways in dendritic spines. (Guidotti, 2016)

Reelin and Neuropsychiatric Disease

Reelin is thought to be involved in the pathogenesis of various brain diseases. As a part of the apolipoprotein E (apoE) biochemical pathway, studies have shown that reelin is involved in the pathogenesis of Alzheimer's disease (AD). In addition, it has been proven that point mutations in the RELN gene cause autosomal recessive anencephaly with cerebellar hypoplasia (LCH). Low expression of Reelin can be observed in some neuropsychiatric diseases, such as schizophrenia, bipolar disorder, and autism. In a heterozygous mutant mouse model, a 50% reduction in reelin expression causes behavioral and anatomical abnormalities consistent with schizophrenia and autism.

Brain magnetic resonance imaging of RELN-associated lissencephaly with cerebellar hypoplasia compared to classical lissencephaly. Fig.2 Brain magnetic resonance imaging of RELN-associated lissencephaly with cerebellar hypoplasia compared to classical lissencephaly. (Chang, et al., 2007)

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References

  1. Chang, BS.; et al. The role of RELN in lissencephaly and neuropsychiatric disease. Am J Med Genet B Neuropsychiatr Genet. 2007;144:58-63.
  2. Guidotti, A.; et al. Epigenetic RELN dysfunction in schizophrenia and related neuropsychiatric disorders. Frontiers in cellular neuroscience. 2016 Apr 5;10:89.
For research use only. Not intended for any clinical use.