Disrupted in schizophrenia 1: building brains and memories

Trends Mol Med. 2006 Jun;12(6):255-61. doi: 10.1016/j.molmed.2006.04.009. Epub 2006 May 6.

Abstract

Schizophrenia and bipolar affective disorder are common, debilitating, and poorly understood and treated disorders. Both conditions are highly heritable. Recent genetic studies have suggested that the gene disrupted in schizophrenia 1 (DISC1) is an important risk factor. DISC1 seems to have a key role in building the brain and memories by interacting with other proteins, including nuclear distribution E-like protein and phosphodiesterase 4B. Here, we review the current knowledge, highlight some key unanswered questions and propose ways forward towards a better understanding of normal and abnormal brain development and function. In the long term, this might lead to the discovery of drugs that are more efficacious and safer than currently available ones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / genetics
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / enzymology*
  • Bipolar Disorder / genetics
  • Brain / drug effects
  • Brain / enzymology*
  • Brain / growth & development
  • Carrier Proteins / metabolism
  • Cyclic AMP / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Genetic Predisposition to Disease*
  • Humans
  • Memory Disorders / drug therapy
  • Memory Disorders / enzymology*
  • Memory Disorders / genetics
  • Models, Animal
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • RNA, Messenger
  • Schizophrenia / drug therapy
  • Schizophrenia / enzymology*
  • Schizophrenia / genetics

Substances

  • Antipsychotic Agents
  • Carrier Proteins
  • DISC1 protein, human
  • DISC2 gene product, human
  • NDEL1 protein, human
  • Nerve Tissue Proteins
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4