Is Cholesterol the Key Factor for Autism? |Biomedgrid

It is hard to reconcile the many genetic and environmental risk factors for ASD [1, 2] to a single mechanism. However, modulation of transmembrane signaling by cholesterol and/or glycosphingolipids (GSLs), both enriched in lipid rafts, and their interlinked metabolism [3] , could provide the basis of such an all-encompassing axis. Membrane cholesterol is important in neuronal development. 25% of the body's cholesterol is in myelin. Most GSLs are also in brain, particularly gangliosides, as the name implies. Surprisingly, the neuron distribution of cholesterol (and GSLs) remains poorly defined. Abnormal cholesterol metabolism/transport is associated with many neuropathies [4] -Alzheimer's [5], Parkinson's [6] ,epilepsy [7] and lysosomal storage diseaneuropathies [8, 9] . GSL biosynthesis is central in neuronal development [10] , particularly myelination [11] , and is also aberrant in neurological disease [9, 12, 13]. Cholesterol/GSL complex Membrane cholesterol and GSLs accumulate in lipid rafts, ubiquitous eukaryotic signaling foci, central to many pathways, particularly, in this context, neurotransmitter signaling [14] . Rafts are more ordered than non-raft membranes due to the rigid character of both GSLs and cholesterol.