Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
Laboratory of Molecular and Functional Neurobiology, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
Ageing Res Rev. 2017 Jul;36:137-148. doi: 10.1016/j.arr.2017.03.003. Epub 2017 Mar 18.
α-Klotho is well described as an anti-aging protein, with critical roles in kidney function as a transmembrane co-receptor for FGF23, and as a soluble factor in serum. α-Klotho is also expressed in the choroid plexus, where it is released into the cerebrospinal fluid. Nonetheless, α-Klotho is also expressed in the brain parenchyma. Accumulating evidence indicates that this pool of α-Klotho, which we define as brain α-Klotho, may play important roles as a neuroprotective factor and in promoting myelination, thereby supporting healthy brain aging. Here we summarize what is known about brain α-Klotho before focusing on the outstanding scientific questions related to its function. We believe there is a need for in vitro studies designed to distinguish between brain α-Klotho and other pools of α-Klotho, and for a greater understanding of the basic function of soluble α-Klotho. The mechanism by which the human KL-VS variant affects cognition also requires further elucidation. To help address these questions we suggest some experimental approaches that other laboratories might consider. In short, we hope to stimulate fresh ideas and encourage new research approaches that will allow the importance of α-Klotho for the aging brain to become clear.
α-klotho 被很好地描述为一种抗衰老蛋白，在肾脏功能中作为 FGF23 的跨膜共受体，以及作为血清中的可溶性因子，起着关键作用。α-klotho 也在脉络丛中表达，在那里它被释放到脑脊液中。尽管如此，α-klotho 也在脑实质中表达。越来越多的证据表明，这部分α-klotho，我们定义为脑α-klotho，可能作为一种神经保护因子发挥重要作用，并促进髓鞘形成，从而支持健康的大脑衰老。在这里，我们总结了已知的脑α-klotho，然后重点介绍了与其功能相关的突出科学问题。我们认为需要进行体外研究，以区分脑α-klotho 和其他 pools 的 α-klotho，并更深入地了解可溶性α-klotho 的基本功能。人类 KL-VS 变体影响认知的机制也需要进一步阐明。为了帮助解决这些问题，我们提出了一些实验方法，其他实验室可能会考虑。简而言之，我们希望激发新的想法，并鼓励新的研究方法，以使 α-klotho 对衰老大脑的重要性变得清晰。
