ABSTRACT
SHANK3, Reelin, and Serotonin Receptors in Autism .............................. 185 10.9.1 Potential Role of Pten and PI3K/Akt Pathway in Autism .............. 188 10.9.2 Neuroligins and Autism ................................................................. 189 10.9.3 SHANK3 and Autism .................................................................... 189 10.9.4 Reelin and Autism.......................................................................... 190 10.9.5 Serotogenic Receptors and Autism ................................................ 190 10.9.6 Evidence of Altered Levels of Bcl2 and p53
(Markers of Apoptosis) in the Brains of Autism Subjects ............. 191
10.10 Oxidative Stress, In ammation, and Cell Signaling ................................... 192 10.10.1 Oxidative Stress in Autism ............................................................ 192 10.10.2 Cytokines, In ammation, and Autism ........................................... 194
10.11 Lipid Rafts and Disorders of the Brain ....................................................... 195 10.12 Conclusions ................................................................................................. 195 References .............................................................................................................. 196
Membrane lipids play an important role in the control of cellular functions. In this chapter, we present evidence that autism spectrum disorders (ASD) are associated with abnormalities in lipid metabolism, membrane-associated proteins, and signal transduction. Altered levels of amino-glycerophospholipids (AGP) in the membrane, increased peroxidation of lipids, and decreased membrane uidity in autism suggest that membrane signaling may be affected in autism. Increased phospholipase A2 (PLA2) activity in the blood and lymphoblasts of autistic subjects suggests that this lipid-metabolizing enzyme may be affected in autism. If membrane lipids abnormalities occur in autism, then lipid rafts, membrane domains with a strong af nity for signaling molecules, may also be involved in the etiology of autism. An association of phosphatidylinositol 3-kinase (PI3K) gene in autism; decreased activity of protein kinase C (PKC); increased activity of protein kinase A (PKA) in the lymphoblasts from autistic subjects; altered brain levels of Bcl2 and p53 involved in apoptosis; in ammation and altered levels of cytokines; and mutational changes in the proteins involved in cell signaling such as neuroligins, Pten, SHANK3, Wnt, reelin, and voltage-dependent calcium channels suggest impairment in signal transduction in autism. These abnormalities in the signal system may account for some of the structural changes and cognitive de cits in the brains of individuals with autism.
