Child Neuropsychiatry Unit, Azienda Sanitaria Locale (ASL) n°5 Oristano, Italy ; Department of Clinical and Experimental Medicine and Pharmacology, University of Messina Messina, Italy.
Front Physiol. 2013 Jan 4;3:486. doi: 10.3389/fphys.2012.00486. eCollection 2012.
Neurodegeneration, a common feature for many brain disorders, has severe consequences on the mental and physical health of an individual. Typically human neurodegenerative diseases are devastating illnesses that predominantly affect elderly people, progress slowly, and lead to disability and premature death; however they may occur at all ages. Despite extensive research and investments, current therapeutic interventions against these disorders treat solely the symptoms. Therefore, since the underlying mechanisms of damage to neurons are similar, in spite of etiology and background heterogeneous, it will be of interest to identify possible trigger point of neurodegeneration enabling development of drugs and/or prevention strategies that target many disorders simultaneously. Among the factors that have been identified so far to cause neurodegeneration, failures in cholesterol homeostasis are indubitably the best investigated. The aim of this review is to critically discuss some of the main results reported in the recent years in this field mainly focusing on the mechanisms that, by recovering perturbations of cholesterol homeostasis in neuronal cells, may correct clinically relevant features occurring in different neurodegenerative disorders and, in this regard, also debate the current potential therapeutic interventions.
神经退行性变是许多脑部疾病的共同特征，对个体的身心健康有严重影响。通常，人类神经退行性疾病是破坏性疾病，主要影响老年人，进展缓慢，导致残疾和过早死亡；然而，它们可能发生在任何年龄。尽管进行了广泛的研究和投资，但目前针对这些疾病的治疗干预措施仅针对症状。因此，由于神经元损伤的潜在机制相似，尽管病因和背景不同，确定可能导致神经退行性变的触发点将有助于开发针对多种疾病的药物和/或预防策略。迄今为止，已经确定了许多导致神经退行性变的因素，胆固醇动态平衡的失败无疑是研究最多的因素之一。本综述的目的是批判性地讨论近年来在该领域报道的一些主要结果，主要集中在通过恢复神经元细胞中胆固醇动态平衡的扰动来纠正不同神经退行性疾病中出现的与临床相关特征的机制上，并在这方面，还讨论了当前潜在的治疗干预措施。
