Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia
| Autor: | Joseph T. Coyle, Richard L. Sidman, Brian T. D. Tobe, Aoi Jitsuki-Takahashi, Hiroko Makihara, Fumio Nakamura, Haruko Nakamura, Yoshio Hirayasu, Keisuke Watanabe, Naoya Yamashita, Glenn T. Konopaske, Evan Y. Snyder, Cameron D Pernia, Yoshio Goshima, Munetaka Nomoto, Reina Aoki, Yusuke Saigusa, Toshihiko Baba, Francine M. Benes, Mari Saito |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty collapsin response mediator protein-2 (CRMP2) Nerve Tissue Proteins blood test 03 medical and health sciences 0302 clinical medicine Mediator Internal medicine medicine Biological neural network Blood test Humans Bipolar disorder Multidisciplinary medicine.diagnostic_test business.industry cytoskeleton Biological Sciences medicine.disease dendritic morphology 030104 developmental biology Endocrinology Gene Expression Regulation Schizophrenia Biomarker (medicine) biomarker Intercellular Signaling Peptides and Proteins Collapsin response mediator protein family medicine.symptom Nerve Net business Mania 030217 neurology & neurosurgery Biomarkers Neuroscience Genome-Wide Association Study |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance There are no biomarkers for schizophrenia (SCZ), a disorder of dysfunctional neural networks. We demonstrate that a master regulator of cytoskeleton (“CRMP2”) and, hence, neural circuitry, may form the basis for such a biomarker because its activity is uniquely imbalanced in SCZ patients. We show that SCZ patients are characterized by an excess of active CRMP2 not only in their brains (where it is correlated with dendritic abnormalities) but also in their peripheral blood lymphocytes. The abundance of active CRMP2 and insufficiency of opposing inactive p-CRMP2 likely disrupts neuronal function. Because peripheral blood CRMP2 appears to reflect intracerebral processes, it could form the basis of a rapid, minimally invasive, sensitive, and specific clinical diagnostic aid for SCZ in young patients. There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2’s activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients |
| Databáze: | OpenAIRE |
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