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Deficit in retromer complex function secondary to lower levels of one of its major components, the vacuolar protein sorting 35 (VPS35), has been reported in Alzheimer's disease (AD) brains. VPS35 genetic reduction results in increased Aβ levels and synaptic pathology in mouse models of the disease. However, whether restoration of its levels has an effect on the AD-like phenotype which includes Aβ plaques, tau tangles and memory impairments remain unknown. In this paper, we investigated the effect of VPS35 gene delivery into the central nervous system on the development of the neuropathology and behavioral deficits of the triple transgenic (3xTg) mice. Compared with controls, animals overexpressing VPS35 had an amelioration of spatial learning and working memory, which associated with a significant reduction in Aβ levels and deposition and tau phosphorylation. Additionally, the same animals had a significant improvement of synaptic pathology and neuroinflammation. In vitro study confirmed that VPS35 up-regulation by reducing total levels of APP and results in a significant decrease in its metabolic products. Our results demonstrate for the first time that VPS35 is directly involved in the development of AD-like phenotype, and for this reason should be considered as a novel therapeutic target for AD.
Pubmed ID: 30733594
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsA software program for the Applied Biosystems StepOne and StepOnePlus Real-Time PCR Systems. StepOne software allows the user to open and analyze experiments generated from either the StepOne or the StepOnePlus system. Users can set up experiments, send experiments to the instrument, control the instrument settings, and collect and analyze data.
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