ArticleScientific reports2015
Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson's disease.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- BLOBFISH: bipartite limited subnetworks from multiple observations using breadth-first search with constrained hops.Bioinformatics (Oxford, England) · 2026Article
- Acrolein-Induced Alterations in Morphology and Stress Resilience in hiPSC-Derived Cortical Neurons.Environmental science & technology · 2025Article
- A Multi-Modal Graph Neural Network Framework for Parkinson's Disease Therapeutic Discovery.International journal of molecular sciences · 2025Article
- A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.Molecular and cellular biochemistry · 2024Review
- A comprehensive review of artificial intelligence and network based approaches to drug repurposing in Covid-19.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- REST Protects Dopaminergic Neurons from Mitochondrial and α-Synuclein Oligomer Pathology in an Alpha Synuclein Overexpressing BAC-Transgenic Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Evolution of Sequence-based Bioinformatics Tools for Protein-protein Interaction Prediction.Current genomics · 2020Review
- Systems Biology Approaches Toward Understanding Primary Mitochondrial Diseases.Frontiers in genetics · 2019Review
- A nonparametric significance test for sampled networks.Bioinformatics (Oxford, England) · 2018Article
- The Effect of Fucoidan on Cellular Oxidative Stress and the CatD-Bax Signaling Axis in MN9D Cells Damaged by 1-Methyl-4-Phenypyridinium.Frontiers in aging neuroscience · 2018Article
- Advantages of Structure-Based Drug Design Approaches in Neurological Disorders.Current neuropharmacology · 2017Review
- Astragaloside IV rescues MPPExperimental and therapeutic medicine · 2017Article
- Overexpression of p58ipk protects neuroblastoma against paraquat-induced toxicity.International journal of clinical and experimental pathology · 2017Article
- Biological and Clinical Implications of Comorbidities in Parkinson's Disease.Frontiers in aging neuroscience · 2017Review
- Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology.Frontiers in aging neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson's disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP(+). Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP(+) model. We hypothesised that analysis of protein-protein interaction networks modelling MPP(+) toxicity could identify proteins critical for mediating MPP(+) toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP(+) toxicity) enabled us to identify four proteins predicted to be key for MPP(+) toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP(+) toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP(+) toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.