ABSTRACT
Channel Function ........................................................................................ 212 11.6 Other Defects in the Calcium Signaling Pathway in Autism ...................... 214 11.7 Calcium Signaling Dysfunction Causes Defects in Neurosecretion ........... 215 11.8 Family of Autism-Related Diseases with Defective Neuronal
Calcium Signaling ....................................................................................... 216 11.9 Pharmacogenetic Calcium Signaling Abnormalities .................................. 218 11.10 Conclusion ................................................................................................... 218 Acknowledgment ................................................................................................... 219 References .............................................................................................................. 219
There are several suggestions in the literature that oxidative stress and mitochondrial function are abnormal in autism. However, these defects produce such global perturbations of cellular homeostasis that it is dif cult to discern the critical pathway leading to the disease phenotype. Resolving this pathway is important
since it provides the most promising target for novel drug development. Since most reactive oxygen species (ROS) arise as by-products of electron transport and oxidative phosphorylation, primary mitochondrial defects are a likely source of ROS. Certainly, genetic defects in mitochondrial function do impose a massive oxidative stress. In the same fashion in which there have been many hints of abnormal ROS levels in autism, many disparate clues have recently come to suggest that abnormal neuronal calcium signaling also plays a role in autism. This is a process recently recognized to be under mitochondrial regulation and capable of disrupting neuronal synaptic function and hence behavior. Therefore, a body of evidence now suggests that calcium signaling abnormalities are a fundamental pathway perturbed in autism, with many lesions arising from primary defects in mitochondrial function, but with other lesions primarily perturbing other components of the calcium signaling pathway and only secondarily impairing mitochondrial function.
