Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
Cell Tissue Res. 2012 Jan;347(1):291-301. doi: 10.1007/s00441-011-1230-6. Epub 2011 Aug 31.
Alzheimer's disease (AD) is a neurodegenerative disorder that affects about 35 million people worldwide. Current drugs for AD only treat the symptoms and do not interfere with the underlying pathogenic mechanisms of the disease. AD is characterized by the presence of β-amyloid (Aβ) plaques, neurofibrillary tangles, and neuronal loss. Identification of the molecular determinants underlying Aβ-induced neurodegeneration is an essential step for the development of disease-modifying drugs. Recently, an impairment of the transforming growth factor-β1 (TGF-β1) signaling pathway has been demonstrated to be specific to the AD brain and, particularly, to the early phase of the disease. TGF-β1 is a neurotrophic factor responsible for the initiation and maintenance of neuronal differentiation and synaptic plasticity. The deficiency of TGF-β1 signaling is associated with Aβ pathology and neurofibrillary tangle formation in AD animal models. Reduced TGF-β1 signaling seems to contribute both to microglial activation and to ectopic cell-cycle re-activation in neurons, two events that contribute to neurodegeneration in the AD brain. The neuroprotective features of TGF-β1 indicate the advantage of rescuing TGF-β1 signaling as a means to slow down the neurodegenerative process in AD.
阿尔茨海默病（AD）是一种神经退行性疾病，影响着全球约 3500 万人。目前用于 AD 的药物仅能治疗症状，而不能干预疾病的潜在发病机制。AD 的特征是β-淀粉样蛋白（Aβ）斑块、神经纤维缠结和神经元丢失的存在。确定 Aβ 诱导的神经退行性变的分子决定因素是开发疾病修饰药物的重要步骤。最近，已经证明转化生长因子-β1（TGF-β1）信号通路的损伤是 AD 大脑特有的，特别是在疾病的早期阶段。TGF-β1 是一种神经营养因子，负责启动和维持神经元分化和突触可塑性。TGF-β1 信号的缺乏与 AD 动物模型中的 Aβ 病理学和神经纤维缠结形成有关。TGF-β1 信号的减少似乎既与小胶质细胞的激活有关，也与神经元中细胞周期异位重新激活有关，这两个事件都有助于 AD 大脑中的神经退行性变。TGF-β1 的神经保护特性表明，恢复 TGF-β1 信号作为减缓 AD 神经退行性过程的一种手段具有优势。
