Department of Clinical Genetics, Amsterdam University Medical Centers location VUmc, Amsterdam, The Netherlands.
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Acta Neuropathol Commun. 2020 Sep 3;8(1):153. doi: 10.1186/s40478-020-00996-5.
In the brains of tauopathy patients, tau pathology coincides with the presence of granulovacuolar degeneration bodies (GVBs) both at the regional and cellular level. Recently, it was shown that intracellular tau pathology causes GVB formation in experimental models thus explaining the strong correlation between these neuropathological hallmarks in the human brain. These novel models of GVB formation provide opportunities for future research into GVB biology, but also urge reevaluation of previous post-mortem observations. Here, we review neuropathological data on GVBs in tauopathies and other neurodegenerative proteinopathies. We discuss the possibility that intracellular aggregates composed of proteins other than tau are also able to induce GVB formation. Furthermore, the potential mechanisms of GVB formation and the downstream functional implications hereof are outlined in view of the current available data. In addition, we provide guidelines for the identification of GVBs in tissue and cell models that will help to facilitate and streamline research towards the elucidation of the role of these enigmatic and understudied structures in neurodegeneration.
在神经tau 病患者的大脑中，tau 病理学与颗粒空泡变性体（GVB）在区域和细胞水平上的存在同时发生。最近的研究表明，细胞内 tau 病理学导致实验模型中 GVB 的形成，从而解释了人类大脑中这些神经病理学标志之间的强相关性。这些新型的 GVB 形成模型为未来的 GVB 生物学研究提供了机会，但也促使我们重新评估以前的尸检观察结果。在这里，我们回顾了神经tau 病和其他神经变性蛋白病中 GVB 的神经病理学数据。我们讨论了细胞内由除 tau 以外的蛋白质组成的聚集物是否也能够诱导 GVB 形成的可能性。此外，鉴于目前可用的数据，概述了 GVB 形成的潜在机制及其下游功能意义。此外，我们还为组织和细胞模型中 GVB 的鉴定提供了指导，这将有助于促进和简化对这些神秘且研究不足的结构在神经退行性变中的作用的研究。
