Research Article
Volume 12 Issue 9 - 2020
Increased MKK3 Correlates with GSK3A and P38 Concentrations in Children with Autism
AJ Russo1*, Albert Mensah2 and Judith Bowman2
1Retired Visiting Assistant Professor of Biology, Drew University, Madison, NJ and Research Director, Mensah Medical Center, Warrenville, Il, USA
2Mensah Medical Center, Warrenville, Il, USA
*Corresponding Author: AJ Russo, Retired Visiting Assistant Professor of Biology, Drew University, Madison, NJ and Research Director, Mensah Medical Center, Warrenville, Il, USA.
Received: June 24, 2020; Published: August 10, 2020


GSK3A (Glycogen synthase kinase 3-alpha), MKK3 (mitogen-activated protein kinase kinase 3) and P38 (P38 mitogen-activated protein kinases) all function in glucose metabolism. GSK3 acting upon glycogen synthase. MKK3 catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase P38 and P38 regulates the expression of GLUT (glucose transporter). In this study we measured the concentration of MKK3, P38 and Insulin in an autistic group and controls and compared these concentrations to GSK3A and the concentrations of each other. We found that, like GSK3A, MKK3 is significantly higher in the autistic group and MKK3 levels correlate significantly with the GSK3A levels. We also found that Both MKK3 and GSK3A concentrations correlated significantly with P38 levels in these patients. These results support a role for glucose membrane transport dysfunction in the etiology of autism.

Keywords: GSK3A (Glycogen Synthase Kinase 3-Alpha); MKK3 (Mitogen-Activated Protein Kinase Kinase 3); P38 (P38 Mitogen-Activated Protein Kinases); GLUT (Glucose Transporter)


  1. DiCicco-Bloom E., et al. “The developmental neurobiology of autism spectrum disorder”. The Journal of Neuroscience 26 (2006): 6897-6906. 
  2. Llaneza DC., et al. “Communication, interventions, and scientific advances in autism: a commentary”. Physiology and Behavior 100 (2010): 268-276. 
  3. Lai MC., et al. “Autism”. Lancet 383 (2014): 896-910. 
  4. DiCicco-Bloom E., et al. “The developmental neurobiology of autism spectrum disorder”. The Journal of Neuroscience 26 (2006): 6897-6906. 
  5. Macfabe DF. “Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders”. Microbial Ecology in Health and Disease 23 (2012): 19260. 
  6. Bhandari R and Kuhad A. “Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders”. Life Sciences 141 (2015): 156-169. 
  7. Chan-Hui PY and Weaver R. "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades". Biochemical Journal 336.3 (1999): 599-609.
  8. Raingeaud J., et al. “MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway”. Molecular and Cellular Biology 16.3 (1996) 1247-1255.
  9. Kurata S. "Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress". The Journal of Biological Chemistry 275.31 (2000): 23413-23416.
  10. Fujishiro M., et al. “MKK6/3 and p38 MAPK Pathway Activation Is Not Necessary for Insulin-induced Glucose Uptake but Regulates Glucose Transporter Expression”. The Journal of Biological Chemistry 276 (2001): 19800-19806.
  11. Beurel E., et al. “Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases”. Pharmacology and Therapeutics 148 (2015): 114-131.
  12. Markussen LK., et al. “GSK3 is a negative regulator of the thermogenic program in brown adipocytes”. Scientific Reports 8 (2018): 3469.
  13. Thornton TM., et al. “Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation”. Science 320 (2008): 667-670.
  14. Beurel E., et al. “Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases”. Pharmacology and Therapeutics (2015): 114-131.
  15. C Montessuit., et al. “Regulation of glucose transporter expression in cardiac myocytes: p38 MAPK is a strong inducer of GLUT4”. Cardiovascular Research 64 (2004): 94-104.
  16. MF Riera., et al. “Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivation”. The American Journal of Physiology-Endocrinology and Metabolism 297 (2009): E907-E914.
  17. Igarashi M., et al. “Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways”. Journal of Clinical Investigation 103.2 (1999): 185-195. 
  18. Russo A., et al. “Increased Glycogen Synthase Kinase 3 Alpha (GSK3A) in Children with Autism”. EC Paediatrics 9.2 (2020): 01-05.
Citation: AJ Russo., et al. “Increased MKK3 Correlates with GSK3A and P38 Concentrations in Children with Autism”. EC Neurology 12.9 (2020): 25-30.

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