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
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 ResearchMeSH KeywordsAmyotrophic Lateral SclerosisAnimalsAxonsCells, CulturedCytoplasmic GranulesDNA-Binding ProteinsHumansMotor NeuronsMutationRatsRats, Sprague-DawleyRibonucleoproteinsViscosityConceptsRNA-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