Images were all ob tained inhibitor licensed with the same acquisition parameters. The images were similarly processed with ImageJ software before being used for quantification the brightness contrast of all control images was optimized manually to eliminate the background and to ma imize the signal. The means of the minimum and ma imum intensities were then calculated in the con trol condition, after which these settings were applied to all images. The images of the three synuclein Tubulin MAP2 stainings were merged and the resulting image was used to define the zone where hippocampal dendrites were sufficiently innervated by cortical fibres. synuclein MAP2 merges were then used for quantification. Quantification of Tau phosphorylation Tau phosphorylation was assessed by counting the number of neurons presenting pTau levels above a fi ed threshold.

Images were all obtained using the same acquisition param eters. The images were similarly processed with ImageJ soft ware before being used for quantification the brightness contrast of all control images was optimized manually to eliminate the background and to ma imize the signal. The means of the minimum and ma imum intensities were then calculated in the control condition, after which these set tings were applied to all images. All pTau images were then processed with the Lookup Tables, fire plugin to visualize the intensity of pTau staining with pseudo colours. The number of neurons above a fi ed colour threshold was then counted and normalized by the total number of neurons to have the percentage of hyperphosphorylated tau neurons.

Introduction Proteoglycans are glycoconjugates composed of a core protein backbone and numerous glycosaminoglycan side chains, which determine the fluid and electrolyte balance and the elasticity of articular cartilage and provide the living space of chondrocytes through interact with the collagen network. Thus, PGs are essential in maintaining cartilage homeostasis. Loss of PGs would lead to the imbalance of cartilage homeostasis, which further accelerates the degeneration of cartilage matri and the apoptosis of chondrocytes, and finally triggers the pathogenesis of osteoarthritis, a chronic and degenerative arthritis with a high prevalence in the elderly. UDP glucose dehydrogenase catalyzes the transformation of UDP glucose to UDP glucuronic acid, a key precursor for the synthesis of the GAG Carfilzomib chain in PGs. Stimulating UGDH enzyme activety with transforming growth factor B resulted in the enhanced GAG synthesis in articular chondrocytes. However, whether UGDH is indispensable in the PGs synthesis of articular chondrocytes and whether UGDH is also involved in the pathogenesis of OA still remain unclear.