Lipid Signalling in the Pathology of Autism Spectrum Disorders

Fatty acids are the simplest type of lipids that serve as building blocks for more complex lipids such as phospholipids, cholesterol, and vitamin E, which are integral to cell membranes (Fig. 1). Abnormal metabolism and imbalances of these three complex lipids have all been associated with autism spectrum disorders (ASDs) and will be outlined in following sections. Fatty acids can be saturated, monounsaturated, or polyunsaturated; the latter will be elaborated upon due to its link with ASDs. Essential fatty acids (EFAs), also called polyunsaturated fatty acids (PUFAs), play an important role in maintaining the structural and functional integrity of the central nervous system (CNS). They serve as major components of neural cell membrane phospholipids and are necessary for the modulation of ion channels, enzymes, and receptor activity (Boland et al. 2009; Guizy et al. 2008). PUFAs must be obtained through the diet since the ability to synthesize them is limited. The two major types of PUFAs are omega-6 linoleic acid (LA; 18:2n-6) and omega-3 a-linolenic acid (ALA; 18:3n-3), which are converted to arachidonic acid (AA, 20:4n-6) and to eicosapentaenoic acid (EPA, 20:5n-3) or docosahexaenoic acid (DHA, 22:6n-3), respectively (Haag 2003) (Figs. 1 and 2). One of the most commonly derived PUFAs from cell membranes is AA. Through the action of phospholipase A2 (PLA2), an enzyme important for cell membrane maintenance, AA is cleaved from membrane phospholipids and further