BRAIN’S MOLECULAR VELCROLet’s look at some cool proteins called cadherins.These proteins form a veritable molecular Velcro that keepsthe neurons adhering to each other. Indeed withoutcadherins there would be no contact between brain cells andno synapses.Cadherins provide the glue that holds the neurons together
The cadherins have to work hand in hand with the proteinsof the neuronal cytoskeleton, especially actin and themicrotubules in order to ensure proper cell to cell contact.CADHERINS WORK TOGETHER WITH THE PROTEINS OF THECYTOSKELETON TO ENSURE CELL SHAPE AND CELLULARADHESIONA defect of the cytoskeleton or cadherins could cause theneurons to collapse like a popped balloon. This would leadto the inability of the cadherins to keep the cells in contactwith each other. Indeed the molecular Velcro would fail andthe synapses would break as well.
Reelin is another cool extracellular protein that effectivelylaminates the outer surfaces of the neurons. It controls thefunction of cadherins. And not only that, but also helps theneurons migrate during early development.Why do we care about all this?The reasons we might care are the following: 1. Many discovered genes that are associated with schizophrenia, bipolar disorder or autism spectrum disorders code for the proteins of the cytoskeleton, reelin or cadherins (DISC 1, Neureglin 1, DTNBP1, RGS4, (Tsuyoshi Hattory “Psychosis and Adhesion Molecules”).
FOUR SCHIZOPHRENIA RISK GENES2. Defects of cytoskeleton proteins are involved in other disorders manifested by psychosis such as Alzheimer’s or Huntington’s disease, in addition to schizophrenia, bipolar disorder and autism spectrum disorder. CYTOSKELETAL PROTEINS
3. Reelin gene was found to be defective in schizophrenia as well as the cytoskeletal proteins. (Cátia M Teixeira Neuropsychopharmacology (2011) 36, 2395–2405; doi:10.1038/npp.2011.153; published online 3 August 2011.). Reelin also has a function in neuronal migration andmaturation. 4. Research data demonstrate that there is no active cell death (apoptosis) in schizophrenia, as no caspase 3 can be detected. In spite of this, other markers of neurodegeneration are present such as increased BAX/Bcl-2 ratio.
CASPASE 3 ACTIVATION IS ABSENT IN SCHIZOPHRENIAIn other words all that we learned about schizophrenia fromthe human genom project was that genes associated with itcode for cytoskeletal proteins, neuronal migration, neuronaladhesion and cell lamination. Indeed only the COMPT geneis associated with dopamine.Is it possible that schizophrenia is all about neuronalorthopedics?Is it possible that psychosis is just a common manifestationof various neuronal architectural defects? Just like fever isthe common manifestation of various inflammatoryprocesses.ADONIS SFERA, MD