4. 1 Functional Classifications Of Functional Functions

4.1 Functional classification of dysregulated proteins It was shown that MPS VII is characterized by accumulation of ubiquitin and neurofilament, but not PHF-Ï„, ÃŽ ±-synuclein or apoptosis [20]. Similarly, significant alterations in the ubiquitin-proteasome system (UPS), but not proteins associated with apoptosis or PHF-Ï„ and ÃŽ ±-synuclein, were identified in this study. Previous transcriptomic and proteomic analyses of MPS VII mouse brain identified many dysregulated proteins involved in metabolism and cytoskeleton [21,22]. Additionally, these studies found that neuroinflammation is also upregulated, but not to a large extent. Similar results were observed in this study, indicating the reliability of the proteomics approach. We also examined†¦show more content†¦Dysregulation of cytoskeletal genes has also been seen in MPS I mouse brains [4], MPS IIIB mouse brains [26] and MPS VII dog hearts [27]. Additionally, low density lipoprotein-related protein 1B (LRP1B), dynamin-1 (DMN1) and dynamin-related protein 1 (DNM1L), w hich are involved in the process of endocytosis, are downregulated. Vesicle associated membrane protein 2 (VAMP2) is involved in the targeting and/or fusion of transport vesicles to their target membrane [28]. These results further suggest impaired lysosomal membrane trafficking pathways in MPS VII. Based on previous reports and results in this study, we hypothesize that GAG accumulation leads to alterations in the cytoskeletal system and thereby impairs lysosomal membrane pathways including endocytosis, exocytosis, autophagy and vesicle transport. Notably, endocytosis defects in brain endothelial cells may contribute to low transcytosis, making enzyme replacement therapy more difficult to achieve neurological benefits. Therefore, targeting specific pathways involved in transcytosis may be an effective strategy to enhance enzyme delivery to the brain in lysosomal diseases including MPS VII. 4.1.2 Proteostasis Many neurodegenerative diseases share a common molecular signature: disruption of proteostasis [29]. This often manifests as an accumulation of ubiquitylated proteins, with evidence for a robust contribution toShow MoreRelatedAn Analysis Of A Project On Java Net Beans949 Words   |  4 Pagesto provide a basic and a very easy user interface. The user interface allows the administrator to provide the input of the credit card transactions. From these transactions, outliers are detected. The main objectives of the design are as follows: 1) Allows administrator to provide the input of the transactions. 2) Allows administrator to provide a name for the output transactions. 3) Allows the administrator to detect the outliers. This project is developed in Java. 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