Lussier April L, Weeber Edwin J, Rebeck G William
Department of Molecular Pharmacology and Physiology, USF Health Byrd Alzheimer's Disease Institute, University of South Florida Tampa, FL, USA.
Department of Neuroscience, Georgetown University Washington, DC, USA.
Front Cell Neurosci. 2016 Mar 29;10:75. doi: 10.3389/fncel.2016.00075. eCollection 2016.
Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer's diseases (AD) tissues including cerebral spinal fluid (CSF), showing that levels of Reelin fragments are altered in AD compared to control. Potential key proteases involved in Reelin proteolysis have recently been defined, identifying processes that could be altered in neurodegeneration. Introduction of full-length Reelin and its proteolytic fragments into several mouse models of neurodegeneration and neuropsychiatric disorders quickly promote learning and memory. These findings support a role for Reelin in learning and memory and suggest further understanding of these processes are important to harness the potential of this pathway in treating cognitive symptoms in neuropsychiatric and neurodegenerative diseases.
Reelin是一种神经发育蛋白，对成人突触可塑性以及学习和记忆很重要。最近的证据表明，Reelin蛋白水解在正常信号传导和认知功能中具有重要意义。对神经退行性变和认知功能障碍中Reelin蛋白水解功能失调的支持来自对阿尔茨海默病（AD）组织（包括脑脊液（CSF））的尸检分析，结果显示与对照组相比，AD中Reelin片段的水平发生了改变。最近已经确定了参与Reelin蛋白水解的潜在关键蛋白酶，从而明确了在神经退行性变中可能发生改变的过程。将全长Reelin及其蛋白水解片段引入几种神经退行性变和神经精神疾病的小鼠模型中，能迅速促进学习和记忆。这些发现支持了Reelin在学习和记忆中的作用，并表明进一步了解这些过程对于利用该途径治疗神经精神疾病和神经退行性疾病中的认知症状的潜力很重要。
