Lee Ryan W Y, Tierney Elaine
Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, 716 North Broadway Street, Baltimore, MD 21205, USA.
Autism Res Treat. 2011;2011:653570. doi: 10.1155/2011/653570. Epub 2011 Apr 27.
A possible role for sterols in the development of autism spectrum disorder (ASD) has not been proven, but studies in disorders of sterol biosynthesis, chiefly Smith-Lemli-Opitz syndrome (SLOS), enable hypotheses on a causal relationship to be discussed. Advances in genetic technology coupled with discoveries in membrane physiology have led to renewed interest for lipids in the nervous system. This paper hypothesizes on the role of sterol dysfunction in ASD through the framework of SLOS. Impaired sonic hedgehog patterning, alterations in membrane lipid rafts leading to abnormal synaptic plasticity, and impaired neurosteroid synthesis are discussed. Potential therapeutic agents include the development of neuroactive steroid-based agents and enzyme-specific drugs. Future investigations should reveal the specific mechanisms underlying sterol dysfunction in neurodevelopmental disorders by utilizing advanced imaging and molecular techniques.
目前尚未证实甾醇在自闭症谱系障碍（ASD）发展过程中发挥作用，但对甾醇生物合成紊乱疾病（主要是史密斯-勒米-奥皮茨综合征，简称SLOS）的研究，使得人们能够探讨关于因果关系的假说。基因技术的进步以及膜生理学领域的发现，引发了人们对神经系统中脂质的新兴趣。本文通过SLOS框架对甾醇功能障碍在ASD中的作用进行了假设。文中讨论了音猬因子信号模式受损、膜脂筏改变导致突触可塑性异常以及神经甾体合成受损的情况。潜在的治疗药物包括开发基于神经活性甾体的药物和酶特异性药物。未来的研究应通过利用先进的成像和分子技术，揭示神经发育障碍中甾醇功能障碍的具体机制。
