Reelin

   The latest protein implicated in the search for the cause of Autism has been reelin. [FEAT, April 29, 2001; Persico et al, 2001)

   Reelin is a secreted extracellular protein that binds to the very low density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2) on the surface of neurons (Keshvara et al, 2001). Reelin and dab1 genes are necessary for appropriate neuronal migration and lamination during brain development (Alvarez-Dolado et al, 1999).

   Apparently - as it has been shown by Fatemi, et al that reelin levels are lowered in children with Autism, and the reelin gene continues to be expressed throughout life - it potentially gives pharmaceutical industry its first “target” for an autism medication, so FEAT 

   Unfortunately, once again a whole team of 22 researchers is/was apparently unaware of the fact that reelin and dab1 is regulated by thyroid hormones, a finding first published in 1999 by Alvarez-Dolado et al., in  the Journal of Neurosciences.[LINK}

   In post mortem studies of autistic brains, researchers at the University of Minnesota (Fatemi, et al) found a 43% reduction in reelin levels in the Purkinje cells of the cerebellum compared to non-autistic brains.

   Purkinje cells are, of course, regulated by thyroid hormones as well.

   Other  recent studies have shown that tyrosine phosphorylation is critical for dab1 function (Keshvara et al, 2001).

From the FEAT letter:

•    In a surprise finding from an international research team led by researchers at the Campus BioMedico University in Rome, Italy, Drs. Flavio Keller and Antonio Persico announced the discoveiy of a gene that may increase the risk of a child's developing autism three-fold. The gene, which produces the protein reelin, has recently been associated with bipolar disorder and schizophrenia.
        The reelin gene is known to be involved in proper lamination"-or layering-of brain cells in utero.
         But unlike many developmental genes, the reelin gene continues to be expressed throughout life, potentially giving the phannaceutical industry its first "target" for an autism medication. If reelin proves to be important in autism, pharmacologists can attempt to create medications that manipulate reelin activity in the brain.
         Researchers do not know what function the protein performs in the postnatal brain. Some believe it is critical to neural plasticity and learning.
         The finding surprised observers because the Italian team was not studying reelin. As part of a larger study of autism and serotonin, they were attempting to replicate work by Karl Reichelt of Norway finding an abnormal presence of peptides-small pieces of proteins-in the urine of autistic children.
        But Keller and Persico could not find Reichelt's peptides in their subjects. When Dr. Reichelt supplied his original samples for re-testing, two laboratories were unable to identify the peptides in Reichelt's samples, either.
        For most researchers the study would have ended there. But it didn't.
      While waiting for the third and final set of lab results, Keller and Persico-convinced the peptides had to be present-hit upon the idea of checking them against the vast library of known human proteins.
         When they found that the only protein containing both peptides was reelin, a protein involved in neurodevelopment, they knew they had struck gold.
         Because the gene for reelin is known, they could examine it in people with autism. Twenty percent of their autistic population, they discovered, carried extra-long versions of the gene. The long variant would be expected to result in a reduction of reelin in the brain.
         The findings, published in the March issue of Molecular Psychiatry, represent the second autism gene to be reported in a fOur-month period. "This is an unprecedented rate of progress for a complex disorder," said Dr.Eric London, Director of Medical Affairs for the National Alliance for Autism Research, which funded the research. "Geneticists estimate as many as 15 different genes may put children at risk of developing autism. To have two strong gene studies published in four months is nothing short of miraculous."
         The National Alliance for Autism Research was founded in 1994 to fund biomedical research into the causes, prevention, treatmfnt and cure of autism and related disorders. Since 1997, NAAR has committed more than $3 million in grants to 50 scientists in the United States, Canada, Italy, Spain and Russia. This year alone, NAAR committed more than $1.5 million in research grants to 20 scientists in the United States and Europe. For more information about NAAR and autism, please log onto NAAR's website at www.naar.org.

Comment: Once again, because hardly any scientist seems to be familiar with research in other fields, the most obvious association is overlooked. It is shocking to see how much research money is plainly being wasted. Even though reduced levels of reelin are clearly shown in thyroid hormone (T3) deficiency - and periods of greatest sensitivity identified - no research is conducted in this field - instead research will now begin on how the pharmaceuticals could raise these lowered reelin levels...

also see: Purkinje Cells ; NGF ; etc.