2024
Ataxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons
Wijegunawardana D, Nayak A, Vishal S, Venkatesh N, Gopal P. Ataxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons. Developmental Cell 2024 PMID: 39419034, DOI: 10.1016/j.devcel.2024.09.023.Peer-Reviewed Original ResearchRNA-binding proteinsAtaxin-2PolyQ expansionTDP-43Like-SmLocal translationAmyotrophic lateral sclerosisDNA-binding proteinsTransactive response DNA-binding proteinLocalization of mRNAAssociated with increased riskRNA metabolismCytoskeletal mRNAsMRNA transportPolyglutamine expansionRNP condensatesMotor neuron axonsRegulatory functionsRibonucleoproteinMotor neuron integrityNeuronal integrityCortical neuronsLiquid-like propertiesNeuronal axonsMotilityRational 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 ResearchConceptsMolecular 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
2023
Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders
Naskar A, Nayak A, Salaikumaran M, Vishal S, Gopal P. Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders. Frontiers In Molecular Neuroscience 2023, 16: 1242925. PMID: 37720552, PMCID: PMC10502346, DOI: 10.3389/fnmol.2023.1242925.Peer-Reviewed Original ResearchAberrant phase transitionsMRNA transportFormation of ribonucleoproteinMembrane-less organellesPathogenic protein aggregationStress granule assemblyALS/frontotemporal dementiaSynaptic functionNeurodegenerative diseasesProcessing bodiesCajal bodiesRNA processingHigher-order structureSpatiotemporal regulationStress granulesTransport granulesAmyotrophic lateral sclerosisGranule assemblyProtein aggregationBiomolecular condensatesMRNA stabilityGene expressionLocal translationPhysiological functionsRBPs