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.

中文翻译：

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解开神经退行性蛋白病中的颗粒-肺泡变性体的起源和功能。

在tauopathy患者的大脑中，tau病理与区域和细胞水平上的颗粒-肺泡变性体（GVBs）一致。最近，研究表明，细胞内tau病理会在实验模型中引起GVB的形成，从而解释了人脑中这些神经病理学特征之间的强相关性。这些新颖的GVB形成模型为将来的GVB生物学研究提供了机会，同时也敦促重新评估以前的验尸观察。在这里，我们审查在taopathies和其他神经退行性蛋白质病中GVBs的神经病理学数据。我们讨论了由tau以外的蛋白质组成的细胞内聚集体也能够诱导GVB形成的可能性。此外，鉴于当前可获得的数据，概述了GVB形成的潜在机理及其​​下游功能含义。此外，我们提供了在组织和细胞模型中鉴定GVB的指导方针，这将有助于促进和简化有关阐明这些神秘且研究不足的结构在神经变性中的作用的研究。