Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alternations in CNS Development
Revised final rept. 15 Sep 2008-14 Sep 2012
ROCHESTER UNIV NY
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The goals of our work are to develop means of identifying cells, and individuals, that present with a more basal oxidized redox state and to identify molecular mechanisms that functionally integrate such an oxidized state with observations that the multiple environmental insults suggested to be involved in autism pathogenesis also occur in many children that do not develop ASD. This suggests there is an underlying vulnerability phenotype that makes some children more vulnerable to such stressors. The regulatory pathway that we discovered to be central to redox-based modulation of cell division, differentiation and survival affects multiple cellular functions that appear to be related to the pathological changes seen in the CNS of children with autism. Moreover, the integration of these findings with the Nrf2 pathway provides mechanisms that may provide better markers of a more oxidative state and have the added value of explaining why the more oxidized cells of an individual with ASD do not reset themselves to create a normal redox balance. These discoveries provide new targets for resetting these metabolic problems, and continuation of this work looks likely to identify agents that could be used to address the oxidative abnormalities that look increasingly likely to be relevant to the understanding of ASD pathogenesis.
- Medicine and Medical Research
- Organic Chemistry