Methylglyoxal, advanced glycation end products and autism: Is there a connection?
Section snippets
Background
Autism is a heterogeneous neurodevelopmental disorder defined by a broad spectrum of atypical social, cognitive and verbal behaviors along with repetitive and sometimes self-injurious actions. Despite affecting an increasing number of children, there are no effective treatments for the disorder [1]. Although the exact causes of autism are unknown, many investigators believe that it is likely the result of a combination of genetic vulnerabilities and environmental insults interacting at a
Hypothesis
Based on these observations, I propose that a combination of inborn genetic vulnerabilities affecting GSH metabolism, Glo-1 and/or mitochondrial function coupled with increased dietary exposure to AGEs and/or the AGE precursor MG could lead to neuropathological changes in the brain and the subsequent behavioral deficits that are characteristic of autism.
This hypothesis ties together a number of the observations that have been made regarding the pathophysiological factors underlying autism and
Predictions
Since both obesity and diabetes [34] are associated with higher exposure to AGEs, this hypothesis predicts that there would be an association between these disorders in mothers and higher rates of autism in their offspring. The limited epidemiological studies on this question suggest that this may be the case. First, on a general level, the prevalence of overweight and obesity [52], [53], [54] as well as diabetes [55], [56], [57] in women of child bearing age in the US, Canada and the UK has
Conflict of interest statement
The author declares that there are no conflicts of interest.
Acknowledgments
This work was supported by a grant from the not-for-profit Fritz B. Burns Foundation. The author would like to thank Drs. David Schubert and Michael Nunn for critical reading of the manuscript.
References (62)
- et al.
Autism spectrum disorder
Curr Biol
(2005) - et al.
Oxidative stress in autism
Pathophysiol
(2006) - et al.
Mitochondrial dysfunction in autism spectrum disorders: cause or effect?
Biochim Biophys Acta
(2010) - et al.
Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death
Brain Res Rev
(1997) - et al.
Transitory glutathione deficit during brain development induces cognitive impairment in juvenile and adult rats: relevance to schizophrenia
Neurobiol Dis
(2007) - et al.
Redox regulation of nerve growth factor-induced neuronal differentiation of PC12 cells through modulation of the nerve growth factor receptor, TrkA
Arch Biochem Biophys
(2005) - et al.
Genetic variant of glutathione peroxidase 1 in autism
Brain Dev
(2010) - et al.
A thermolyzed diet increases oxidative stress, plasma a-aldehydes and colonic inflammation in the rat
Chem Biol Interac
(2007) - et al.
Immune dysfunction in autism: a pathway to treatment
Neurotherapeutics
(2010) - et al.
A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases
Am J Clin Nutr
(2010)