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Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation - Relevance to psychiatric and neurodevelopmental illness, and implications for treatment.
Neurobiol Stress
November 2024
School of Life Sciences, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Social isolation is an established risk factor for psychiatric illness, and became increasingly topical with the spread of SARS-CoV-2. We used RNA sequencing (RNA-Seq) to enable unbiased assessment of transcriptomic changes within the prefrontal cortex (PFC) of isolation-reared rats. To provide insight into the relevance of this manipulation for studying human illness, we compared differentially expressed genes (DEGs) and enriched biological functions against datasets involving post-mortem frontal cortical tissue from patients with psychiatric and neurodevelopmental illnesses.
View Article and Find Full Text PDFCACHE Challenge #1: Targeting the WDR Domain of LRRK2, A Parkinson's Disease Associated Protein.
J Chem Inf Model
November 2024
Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
The CACHE challenges are a series of prospective benchmarking exercises to evaluate progress in the field of computational hit-finding. Here we report the results of the inaugural CACHE challenge in which 23 computational teams each selected up to 100 commercially available compounds that they predicted would bind to the WDR domain of the Parkinson's disease target LRRK2, a domain with no known ligand and only an apo structure in the PDB. The lack of known binding data and presumably low druggability of the target is a challenge to computational hit finding methods.
View Article and Find Full Text PDFA network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.
Res Sq
October 2024
Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments are directed at symptoms and lack ability to slow or prevent disease progression. Large-scale genome-wide association studies (GWAS) have identified numerous genomic loci associated with PD, which may guide the development of disease-modifying treatments.
View Article and Find Full Text PDFExpanding drug targets for 112 chronic diseases using a machine learning-assisted genetic priority score.
Nat Commun
October 2024
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Article Synopsis
- Researchers created a machine learning tool called ML-GPS to help find genetic factors linked to chronic diseases, aiding in drug development.
- This tool combines genetic data from the UK Biobank with advanced modeling techniques to predict disease phenotypes and their associations with various genetic variants.
- ML-GPS significantly increases the number of potential drug targets and can identify both established and promising target-disease relationships, including those related to Parkinson's and cardiovascular diseases.
Designing the First Trials for Parkinson's Prevention.
J Parkinsons Dis
October 2024
Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
For decades the greatest goal of Parkinson's disease (PD) research has often been distilled to the discovery of treatments that prevent the disease or its progression. However, until recently only the latter has been realistically pursued through randomized clinical trials of candidate disease-modifying therapy (DMT) conducted on individuals after they received traditional clinical diagnosis of PD (i.e.
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