The involvement of Reelin in neurodevelopmental disorders

Neuropharmacology. 2013 May:68:122-35. doi: 10.1016/j.neuropharm.2012.08.015. Epub 2012 Sep 7.

Abstract

Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders. The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities. Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autistic Disorder / genetics*
  • Autistic Disorder / metabolism
  • Brain / metabolism*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cognition
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Reelin Protein
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / metabolism

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Reelin Protein
  • reelin receptor
  • RELN protein, human
  • Serine Endopeptidases