9 research outputs found
Drugst.One -- A plug-and-play solution for online systems medicine and network-based drug repurposing
In recent decades, the development of new drugs has become increasingly
expensive and inefficient, and the molecular mechanisms of most pharmaceuticals
remain poorly understood. In response, computational systems and network
medicine tools have emerged to identify potential drug repurposing candidates.
However, these tools often require complex installation and lack intuitive
visual network mining capabilities. To tackle these challenges, we introduce
Drugst.One, a platform that assists specialized computational medicine tools in
becoming user-friendly, web-based utilities for drug repurposing. With just
three lines of code, Drugst.One turns any systems biology software into an
interactive web tool for modeling and analyzing complex protein-drug-disease
networks. Demonstrating its broad adaptability, Drugst.One has been
successfully integrated with 21 computational systems medicine tools. Available
at https://drugst.one, Drugst.One has significant potential for streamlining
the drug discovery process, allowing researchers to focus on essential aspects
of pharmaceutical treatment research.Comment: 45 pages, 6 figures, 7 table
Mechanisms of Hybrid Oligomer Formation in the Pathogenesis of Combined Alzheimer's and Parkinson's Diseases
Background: Misfolding and pathological aggregation of neuronal proteins has been proposed to play a critical role in the pathogenesis of neurodegenerative disorders. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are frequent neurodegenerative diseases of the aging population. While progressive accumulation of amyloid b protein (Ab) oligomers has been identified as one of the central toxic events in AD, accumulation of a-synuclein (a-syn) resulting in the formation of oligomers and protofibrils has been linked to PD and Lewy body Disease (LBD). We have recently shown that Ab promotes a-syn aggregation and toxic conversion in vivo, suggesting that abnormal interactions between misfolded proteins might contribute to disease pathogenesis. However the molecular characteristics and consequences of these interactions are not completely clear. Methodology/Principal Findings: In order to understand the molecular mechanisms involved in potential Ab/a-syn interactions, immunoblot, molecular modeling, and in vitro studies with a-syn and Ab were performed. We showed in vivo in the brains of patients with AD/PD and in transgenic mice, Ab and a-synuclein co-immunoprecipitate and form complexes. Molecular modeling and simulations showed that Ab binds a-syn monomers, homodimers, and trimers, forming hybrid ringlike pentamers. Interactions occurred between the N-terminus of Ab and the N-terminus and C-terminus of a-syn. Interacting a-syn and Ab dimers that dock on the membrane incorporated additional a-syn molecules, leading to th
Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein
Job file for the creation/design of stained glass from either the Charles J. Connick Studio (1912-1945) or the Charles J. Connick Associates studio (1945-1986). The job file contains a job number, location information, date of completion, size, contact information, price, and a description of the project. This particular job file contains information on a job located at: Valley City, North Dakota. Our Saviour's Lutheran Church