2024
Rational Design of TDP-43 Derived α‑Helical Peptide Inhibitors: An In Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders
Salaikumaran M, Gopal P. Rational Design of TDP-43 Derived α‑Helical Peptide Inhibitors: An In Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders. ACS Chemical Neuroscience 2024, 15: 1096-1109. PMID: 38466778, PMCID: PMC10959110, DOI: 10.1021/acschemneuro.3c00659.Peer-Reviewed Original ResearchMeSH KeywordsAmyotrophic Lateral SclerosisDNA-Binding ProteinsHumansMolecular Docking SimulationPeptidesProtein Conformation, alpha-HelicalConceptsMolecular dynamics simulationsTDP-43 aggregationTDP-43Disordered C-terminal regionDynamics simulationsIntramolecular hydrogen bondsAmyloid-like filamentsPeptide inhibitorRNA/DNA-binding proteinC-terminal regionPathology of neurodegenerative diseasesNeurodegenerative diseasesAggregation of TDP-43Binding affinityStructure-based computational approachDesign of peptide inhibitorsRNA/DNA-bindingLow root-mean-square deviationRNA splicingMRNA transportPeptide-based therapeuticsRoot-mean-square deviationDevelopment of novel therapeuticsFree energy landscapeStructure prediction
2020
RNA-binding proteins in neurological development and disease
Prashad S, Gopal PP. RNA-binding proteins in neurological development and disease. RNA Biology 2020, 18: 972-987. PMID: 32865115, PMCID: PMC8216196, DOI: 10.1080/15476286.2020.1809186.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRNA-binding proteinGene expressionDisease-linked RNA-binding proteinsHigh-throughput transcriptomic analysisRNA processing stepsAberrant RNA metabolismAberrant RNA processingRecent exciting studiesRNA processingRNA metabolismMRNA traffickingAlternative splicingMultifunctional proteinTranscriptomic analysisSplicing misregulationMRNA stabilityMolecular mechanismsProtein resultsNeuronal homeostasisNeurodevelopmental defectsNeuronal proteinsFunctional consequencesPleiotropic effectsSpatiotemporal controlProtein
2017
Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons
Gopal PP, Nirschl JJ, Klinman E, Holzbaur EL. Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e2466-e2475. PMID: 28265061, PMCID: PMC5373408, DOI: 10.1073/pnas.1614462114.Peer-Reviewed Original ResearchConceptsRNA-binding proteinRNP granulesAmyotrophic lateral sclerosis-linked mutationsCritical cellular processesRapid fluorescence recoveryAmyotrophic lateral sclerosisBiophysical propertiesDistinct biophysical propertiesRibonucleoprotein granulesSubcellular contextCellular processesSpecific RNAToxic gainTAR-DNA binding protein 43Superresolution microscopyFluorescence recoveryLiquid-liquid phase separationMutant TDP-43Primary cortical neuronsLiquid-like propertiesTDP-43RNAProteinMutationsAxonal location