Ichthyosis in Sjogren-Larsson syndrome

Sjd-Larsson综合征（SLS）是一种遗传性神经皮肤疾病，由基因突变引起。 ALDH 3A 2基因编码脂肪醛脱氢酶（FATIGUE DEHYDROGENERATION，FATIGUE DH）。SLS的症状包括 鱼鳞病，智力迟钝和痉挛，并被假设为产生于紊乱的代谢， 脂肪醛和前体脂质，如脂肪醇，其不能被β-脱氢酶代谢。 然而，对SLS的潜在生化发病机制和有效治疗方法知之甚少。 疾病缺乏。我们研究的长期目标是了解导致 SLS的症状，以便为受影响的患者开发特定的治疗方法。 为了深入了解SLS的生化和病理异常，我们将广泛描述 一种新的SLS的CDDH缺陷基因敲除小鼠模型的生化和表型特征， 并研究遗传背景对其表型表达的作用。培养的角质形成细胞， 将研究来自C16 OH缺陷小鼠的少突胶质细胞和混合神经元细胞， 特殊脂质异常使用CD 3DH缺陷小鼠和SLS患者的培养细胞，我们将 确定C13 DH是否涉及所产生的脂肪醛和脂肪醇的代谢 由法呢醇、ω-羟基脂肪酸和（R）-三羟甲基喹啉A3制备。这些途径可能适合于 通过饮食调整和药物进行治疗干预。使用免疫学和 化学方法结合质谱分析，我们将鉴定共价修饰的蛋白质 通过脂肪醛在SLS细胞中的作用，以深入了解负责皮肤炎症的致病机制。 和神经系统症状总之，这些研究将定义SLS细胞中出现的异常代谢 并利用第一个SLS动物模型来发现新的致病性 负责皮肤和神经症状的机制。 本研究旨在探讨干燥-拉尔森综合征（SLS），一种遗传性代谢疾病 影响儿童和成人的皮肤和大脑。我们将研究发生在 从病人的皮肤细胞中发现症状的原因，并描述一种新开发的小鼠 与SLS患者有相同的代谢问题，希望能开发出有效的治疗方法。

Sjdgren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH). The symptoms of SLS include chthyosis, mental retardation and spasticity, and are hypothesized to arise from the deranged metabolism of fatty aldehydes and precursor lipids such as fatty alcohols, which cannot be metabolized by FALDH. However, little is known about the underlying biochemical pathogenesis of SLS and effective therapy for the disease is lacking. The long-term goal of our research is to understand the pathogenic mechanisms causing the symptoms of SLS in order to develop specific therapy for affected patients. To gain insight into the biochemical and pathologic abnormalites in SLS, we will extensively characterize the biochemical and phenotypic features of a new FALDH-deficient gene knockout mouse model for SLS, and examine the role of genetic background on its phenotypic expression. Cultured keratinocytes, oligodendrocytes and mixed neuronal cells from FALOH-deficient mice will be investigated to reveal cell- specific lipid abnormalities. Using FALDH-deficient mice and cultured cells from SLS patients, we will determine whether FALDH is implicated in the metabolism of fatty aldehydes and fatty alcohols generated from farnesol, w-hydroxy fatty acids and (R)-trioxilin A3. These pathways are potentially amenable to therapeutic intervention with dietary modification and pharmacologic agents. Using immunologic and chemical methods together with mass spectrometry, we will identify the proteins that are covalently modified by fatty aldehyde in SLS cells to gain insight into the pathogenic mechanisms responsible for the cutaneous and neurologic symptoms. In summary, these studies will define the aberrant metabolism in SLS cells arising from FALDH deficiency and take advantage of the first animal model for SLS to uncover new pathogenic mechanisms responsible for cutaneous and neurologic symptoms. This research is directed at investigating Sjogren-Larsson syndrome (SLS), an inherited metabolic disease affecting the skin and brain of children and adults. We will study the abnormal fat metabolism that occurs in skin cells from patients to discover the cause of the symptoms, and characterize a newly developed mouse that has the same metabolic problem as people with SLS in hopes of developing an effective treatment.