ArticleBiological psychiatry2023
Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Omics research in Parkinson's disease: evolution, integrated analysis, pathogenic mechanisms, biomarkers, and therapeutic targets.Frontiers in molecular neuroscience · 2026Pooled it
- Multi-omics Insights into Oxidative Stress-related Genes and Neurodegenerative Diseases: From Epigenetic Regulation to Pathogenic Pathways.Journal of molecular neuroscience : MN · 2026Article
- Integrated proteomic, transcriptomic, and epigenomic profiling identifies SRA1 as a novel therapeutic target for postpartum depression.Npj mental health research · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Multi-Scale Genetic and Transcriptomic Analyses Identify Druggable Targets for Epilepsy.Current medical science · 2026Article
- Vascular contribution to cognitive impairment and dementia (VCID): proceedings of 2025 workshop of the Jackson Laboratory.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Article
- Mendelian Randomization Analysis of the Brain, Cerebrospinal Fluid, and Plasma Proteome Identifies a Potential Peripheral Biomarker for Isolated REM Sleep Behavior Disorder.Journal of molecular neuroscience : MN · 2026Article
- A Histone Deacetylase Activity Model for the Discovery and Validation of Sepsis Biomarkers.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Exosomal gene-based predictive model and therapeutic target identification for Alzheimer's disease: A bioinformatics analysis.PloS one · 2026Article
- Genetic insights into drug targets for alzheimer's disease: integrative multi-omics analysis.Alzheimer's research & therapy · 2025Article
- Bibliometric analysis and core target identification of network pharmacology on neuroinflammation in central nervous system disorders: Trends, collaborations, and future directions.Neuroprotection (Chichester, England) · 2025Review
- Proteomic landscape of multidimensional aging phenotypes.Genome medicine · 2025Article
- Identifying Key Plasma Proteins in the Onset of Parkinson's Disease: Proteome-Wide Mendelian Randomization and Single-Cell RNA Sequencing Analysis.Molecular neurobiology · 2025Article
- Pyruvate kinase deficiency links metabolic perturbations to neurodegeneration and axonal protection.Molecular metabolism · 2025Article
- A map of enhancer regions in primary human neural progenitor cells using capture STARR-seq.Genome research · 2025Article
- Proteome-wide Mendelian randomization and colocalization analysis identify therapeutic targets for stroke.BMC neurology · 2025Article
- Immune Cell Proteins and Parkinson's Disease: A Mendelian Randomization Analysis of Causal Associations.Brain and behavior · 2025Article
- Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis.Arquivos de neuro-psiquiatria · 2025Article
- Identification of Common Brain Protein and Genetic Loci Between Parkinson's Disease and Lewy Body Dementia.CNS neuroscience & therapeutics · 2025Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNeurodegenerative diseases are among the most prevalent and devastating neurological disorders, with few effective prevention and treatment strategies. We aimed to integrate genetic and proteomic data to prioritize drug targets for neurodegenerative diseases.
methodsWe screened human proteomes through Mendelian randomization to identify causal mediators of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, frontotemporal dementia, and Lewy body dementia. For instruments, we used brain and blood protein quantitative trait loci identified from one genome-wide association study with 376 participants and another with 3301 participants, respectively. Causal associations were subsequently validated by sensitivity analyses and colocalization. The safety and druggability of identified targets were also evaluated.
resultsOur analyses showed targeting BIN1, GRN, and RET levels in blood as well as ACE, ICA1L, MAP1S, SLC20A2, and TOM1L2 levels in brain might reduce Alzheimer's disease risk, while ICA1L, SLC20A2, and TOM1L2 were not recommended as prioritized drugs due to the identified potential side effects. Brain CD38, DGKQ, GPNMB, and SEC23IP were candidate targets for Parkinson's disease. Among them, GPNMB was the most promising target for Parkinson's disease with their causal relationship evidenced by studies on both brain and blood tissues. Interventions targeting FCRL3, LMAN2, and MAPK3 in blood and DHRS11, FAM120B, SHMT1, and TSFM in brain might affect multiple sclerosis risk. The risk of amyotrophic lateral sclerosis might be reduced by medications targeting DHRS11, PSMB3, SARM1, and SCFD1 in brain.
conclusionsOur study prioritized 22 proteins as targets for neurodegenerative diseases and provided preliminary evidence for drug development. Further studies are warranted to validate these targets.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.