Banko Jessica L, Trotter Justin, Weeber Edwin J
Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, University of South Florida, Tampa, FL, USA.
Department of Molecular Pharmacology & Physiology, USF Health Byrd Alzheimer's Research Institute, University of South Florida, 4001 East Fletcher Ave, Tampa, FL 33612, USA.
Future Neurol. 2011 Jan;6(1):113-125. doi: 10.2217/fnl.10.80.
Modern approaches to the investigation of the molecular mechanisms underlying human cognitive disease often include multidisciplinary examination of animal models engineered with specific mutations that spatially and temporally restrict expression of a gene of interest. This approach not only makes possible the development of animal models that demonstrate phenotypic similarities to their respective human disorders, but has also allowed for significant progress towards understanding the processes that mediate synaptic function and memory formation in the nondiseased state. Examples of successful mouse models where genetic manipulation of the mouse resulted in recapitulation of the symptomatology of the human disorder and was used to significantly expand our understanding of the molecular mechanisms underlying normal synaptic plasticity and memory formation are discussed in this article. These studies have broadened our knowledge of several signal transduction cascades that function throughout life to mediate synaptic physiology. Defining these events is key for developing therapies to address disorders of cognitive ability.
现代对人类认知疾病潜在分子机制的研究方法通常包括对经过基因工程改造的动物模型进行多学科检查,这些模型通过特定突变在空间和时间上限制感兴趣基因的表达。这种方法不仅使开发出与各自人类疾病表现出表型相似性的动物模型成为可能,还在理解非疾病状态下介导突触功能和记忆形成的过程方面取得了重大进展。本文讨论了成功的小鼠模型实例,在这些模型中,对小鼠的基因操作导致了人类疾病症状的重现,并被用于显著扩展我们对正常突触可塑性和记忆形成潜在分子机制的理解。这些研究拓宽了我们对几种在整个生命过程中发挥作用以介导突触生理学的信号转导级联反应的认识。明确这些事件是开发治疗认知能力障碍疗法的关键。