PDF(Pubmed)
Abstract：
Neurodegenerative proteinopathies such as Alzheimer\'s Disease are characterized by abnormal protein aggregation and neurodegeneration. Neuroresilience or regenerative strategies to prevent neurodegeneration, preserve function, or restore lost neurons may have the potential to combat human proteinopathies; however, the adult human brain possesses a limited capacity to replace lost neurons. In contrast, axolotls (Ambystoma mexicanum) show robust brain regeneration. To determine whether axolotls may help identify potential neuroresilience or regenerative strategies in humans, we first interrogated whether axolotls express putative proteins homologous to human proteins associated with neurodegenerative diseases. We compared the homology between human and axolotl proteins implicated in human proteinopathies and found that axolotls encode proteins highly similar to human microtubule-binding protein tau (tau), amyloid precursor protein (APP), and β-secretase 1 (BACE1), which are critically involved in human proteinopathies like Alzheimer\'s Disease. We then tested monoclonal Tau and BACE1 antibodies previously used in human and rodent neurodegenerative disease studies using immunohistochemistry and western blotting to validate the homology for these proteins. These studies suggest that axolotls may prove useful in studying the role of these proteins in disease within the context of neuroresilience and repair.
摘要：
神经变性蛋白病如阿尔茨海默病的特征在于异常的蛋白聚集和神经变性。神经弹性或再生策略，以防止神经变性，保留函数，或恢复丢失的神经元可能具有对抗人类蛋白质病的潜力；然而，成年人的大脑替换丢失的神经元的能力有限。相比之下,axolotls（Ambystomamexicanum）显示出强大的大脑再生能力。为了确定axolotls是否有助于识别人类潜在的神经弹性或再生策略，我们首先询问了axolotls是否表达与神经退行性疾病相关的人类蛋白质同源的推定蛋白质。我们比较了与人类蛋白质病有关的人类和axolotl蛋白之间的同源性，发现axolotl编码与人类微管结合蛋白tau（tau）高度相似的蛋白质。淀粉样前体蛋白（APP），和β-分泌酶1（BACE1），这些疾病与阿尔茨海默病等人类蛋白质病密切相关。然后，我们使用免疫组织化学和蛋白质印迹测试了先前在人类和啮齿动物神经退行性疾病研究中使用的单克隆Tau和BACE1抗体，以验证这些蛋白质的同源性。这些研究表明，在神经弹性和修复的背景下，axolotls可能有助于研究这些蛋白质在疾病中的作用。
