MicroRNAs in mouse development and disease

MicroRNAs, small non-coding RNAs which act as repressors of target genes, were discovered in 1993, and since then have been shown to play important roles in the development of numerous systems. Consistent with this role, they are also implicated in the pathogenesis of multiple diseases. Here we review the involvement of microRNAs in mouse development and disease, with particular reference to deafness as an example.     

MicroRNAs in stress signaling and human disease

Disease is often the result of an aberrant or inadequate response to physiologic and pathophysiologic stress. Studies over the last 10 years have uncovered a recurring paradigm in which microRNAs (miRNAs) regulate cellular behavior under these conditions, suggesting an especially significant role for these small RNAs in pathologic settings. Here, we review emerging principles of miRNA regulation of stress signaling pathways and apply these concepts to our understanding of the roles of miRNAs in disease. These discussions further highlight the unique challenges and opportunities associated with the mechanistic dissection of miRNA functions and the development of miRNA-based therapeutics.     

Motor impairment in Alzheimer's disease and transgenic Alzheimer's disease mouse models

In this commentary, we accent the accumulating evidence for motor impairment as a common feature of early Alzheimer's disease (AD) pathology. In addition, we summarize the state of knowledge on this phenotype in experimental mouse models, expressing AD-associated genes like tau or amyloid precursor protein.     

雌激素与阿尔采末病

阿尔采末病（ＡＤ）是一种慢性的大脑神经退行性变性疾病,主要表现为进行性远近记忆力障碍、语言、情感、认知、行为等方面改变。近年研究发现,ＡＤ的发病与雌激素缺乏有密切关系。雌激素可通过多种途径、环节延缓ＡＤ发生、发展。如促进可溶性β－淀粉样蛋白（Ａβ）生成,维持中枢神经元组织结构,影响中枢神经递质含量、酶活性、载脂蛋白Ｅ（ａｐｏＥ）生成及抗氧化等。目前,雌激素作为预防和治疗ＡＤ的药物日益受到重视,可望     

Alzheimer's disease untangled.

The last year has seen major advances in the study of Alzheimer's disease (AD). Four mutations involving amino acid substitutions in exons 16 and 17 of the amyloid precursor protein (APP) gene, have been identified which co-segregate with the disease in some families multiply affected by early onset Alzheimer's disease. These mutations are strongly suggestive of a causative role for the amyloid precursor protein in Alzheimer's disease. Despite their rarity, these mutations are important because they represent the first known cause of Alzheimer's disease. Processing of APP must be central to the pathogenesis of the disease although the precise effects of these amino acid substitutions are not understood. Work is now being undertaken to characterise the processing pathways of APP and to identify other causes of AD. The development of models of AD using the APP mutations offers the possibility of identifying drug targets and developing more effective treatments than are presently available.     

Advances in Alzheimer's disease

The problem of the etiology of Alzheimer's disease has not been solved. But in the past several years there have been significant extensions of our knowledge of the disease and advances in determining the molecular changes underlying the disorder. There is now convincing evidence that the dementia per se is caused by loss of neurons and synapses, particularly in neocortex and hippocampus. The molecular aspects of amyloid and its precursor protein have been defined. The nature of intracellular changes leading to accumulation of the paired helical filament is beginning to be understood. For the first time, putative risk factors can be described in terms of pathogenetic mechanisms. Thus, it may become possible in the not-too-distant future to discover interventions that will slow the progress of this devastating disease.     

阿茨海默氏病研究

阿茨海默氏病（Alzheimer‘s disease,AD）受到科学界的广泛关注。已发现的AD相关基因的突变,只能解释某有族性病例,而至少60％的AD患者没有家族史,对这些散发性AD的病理,van Leeuwen等做了有意义 探索,他们的实验证明,AD脑部存在由于GA缺失造成移码突变的β淀粉样蛋白前体和泛素－B,并推测这种移码突变是AD病理的重要起妈因子。该实验开辟了从蛋白合成错误的角度研究AD的新视点,并为RNA编辑提供了新的类型。