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 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
2019
Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons
Stavoe A, Gopal P, Gubas A, Tooze S, Holzbaur E. Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons. ELife 2019, 8: e44219. PMID: 31309927, PMCID: PMC6634969, DOI: 10.7554/elife.44219.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisAged miceNovel therapeutic targetLate-onset neurodegenerative diseasesAge-associated neurodegenerationAge-related declineAged neuronsRisk factorsLateral sclerosisParkinson's diseaseTherapeutic targetLC3B-positive autophagosomesNeurodegenerative diseasesMammalian neuronsNeuronsSignificant decreaseDiseaseRate of autophagy