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Decrypting a collagen’s role in schizophrenia

Decrypting a collagen's role in schizophrenia

What would be worse than having bad joints? How about schizophrenia and bad joints? To be fair that isn’t what is suggested, but they may, in fact, be linked.  A small peptide generated from a collagen protein may protect the brain from schizophrenia by promoting the formation of neuronal synapses and study may lead to new approaches to treating the mental disorder.

The collagen family of extracellular matrix proteins performs numerous functions in the brain, and mutations in several family members cause neurological diseases in humans. How collagen XIX promotes normal brain function is unknown, but loss of the gene encoding this collagen has been linked to familial schizophrenia.

A team of researchers led by Michael Fox at Virginia Tech Carilion Research Institute has been closely examining collagen XIX. They found that collagen XIX-deficient mice display a number of schizophrenia-related symptoms, including an abnormal startle response and an increased susceptibility to seizures. Schizophrenia has previously been linked to defects in a particular type of interneuron. This interneuron dampens neuronal activity in the brain’s cortex by forming inhibitory synapses with the cell bodies of other neurons. These inhibitory synapses were lost in collagen XIX-deficient mice.

Like similar types of collagen, collagen XIX can be cleaved by extracellular protease enzyme to generate a small signaling peptide called a matricryptin. Jianmin Su and colleagues found that this peptide was sufficient to rescue the formation of inhibitory synapses in neuronal cultures prepared from collagen XIX-deficient mice, apparently by binding and activating a cell adhesion receptor called integrin α5β1.

Fox and colleagues now want to learn more about how collagen XIX’s matricryptin fragment promotes synapse formation.

“We also want to investigate whether the peptide holds any therapeutic potential for any diseases that result for malformed or malfunctioning cortical interneurons,” Fox says.

Su, J., Chen, J., Lippold, K., Monavarfeshani, A., Carrillo, G., Jenkins, R., & Fox, M. (2016). Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex The Journal of Cell Biology, 212 (6), 721-736 DOI: 10.1083/jcb.201509085

2 responses

  1. Megan Worner

    I know that at a neuronal synapse the neurotransmitters are being chemically signaled to receptors, but you are suggesting that because these mice lacked collagen XIX and had inhibitory synapses that these are the causes of schizophrenia? And with the help the peptide matricryptin, the inhibitory synapses can be rescued?


    March 30, 2016 at 9:48 pm

    • Not exactly, mice and humans while similar still are vastly different, so one may not actually apply to the other.

      But over all I think you have the right idea. The study is suggesting that there may be a link to developing schizophrenia and these inhibitory synapses which use a signaling peptide that is derived from that particular type of collagen.

      Moreover that there may be a way to treat the loss of these neurons through introduction of that peptide.

      So interneurons of healthy individuals develop inhibitory synapses, the development of which is effected by, if not regulated by, the peptide and that introduction of the peptide helps interneurons regulate the production of these inhibitory synapses. At least that was what I took away from it, I hope that wasn’t too confusing sometimes I don’t think as linearly as I should.


      April 1, 2016 at 11:22 am

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