Biology subjects

VERMA, S.

Publications and source records attributed to VERMA, S..

6 recordsLinked to original sources

bioRxiv2026

Mitigation of Parkinson's Disease Pathology in C. elegans by Marine Bacterium Kocuria rhizophila via Ferroptosis Suppression

Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by the loss of dopaminergic (DA) neurons and alpha-synuclein aggregation, with ferroptosis playing a critical pathological role. This study investigated the neuroprotective potential of Kocuria rhizophila strain CDMP12, a marine bacterium isolated from the Gulf of Mannar, India, using Caenorhabditis elegans models of PD. Dietary supplementation with K. rhizophila (CDMP12) significantly preserved DA neuron structure, rescued neuro-sensory and motor deficits, and attenuated both alpha-synuclein expression in the C. elegans models. Transcriptomic and qRT-PCR analyses revealed that CDMP12 systematically suppressed ferroptosis by significantly downregulating iron and lipid regulatory genes such as smf-3, ftn-1, and acs-4, while upregulating the protective antioxidant gene gpx-1. Furthermore, BODIPY staining demonstrated that CDMP12 treatment markedly reduced lipid peroxidation, lowering the oxidized-to-non-oxidized lipid ratio in PD worms. Collectively, these findings identify K. rhizophila (CDMP12) as a promising marine-derived neuroprotective candidate that mitigates PD-associated pathology, accompanied by reduced alpha-synuclein burden, preservation of DA neuronal function, and attenuation of ferroptosis-associated molecular and lipid peroxidation signatures.

neuroscience↗

bioRxiv2025

Unveiling the PET plastics degradation potential of the thermostable EstS1 esterase through integrated biochemical, structural, and morphological analyses

Enzymatic polyethylene terephthalate (PET) plastic degradation is a promising approach to combat the exploding plastic pollution. EstS1, a pH-tolerant, thermostable esterase, has been previously recognized for its degradation potential against phthalate diester plasticizers. The present study elucidates the exceptional potential of this enzyme to degrade crystalline PET plastic and its primary intermediate, bis(2-hydroxyethyl)terephthalate (BHET), into terephthalate. Kinetic analyses revealed that EstS1 degrades 75% of BHET in 1h, liberating mono(2-hydroxyethyl) terephthalate (MHET) and terephthalate as end products. The co-crystal structure of wild-type EstS1 with BHET exhibited the electron density of BHET, MHET, and ethylene glycol, including MHET bound at the active site, in a canonical tetrahedral intermediate conformation. The complex structure of BHET with the Ser154Ala mutant of EstS1 further accommodated two BHET molecules, one interacting directly with the catalytic triad and the oxyanion hole. MD simulation analysis revealed highly stable interactions of BHET at the active site of EstS1. Moreover, SEM imaging displayed significant degradation of the crystalline PET plastic film by EstS1 esterase over a period of 15 days, both under controlled and soil-based fluctuating environmental conditions, highlighting its versatility to varying environmental conditions. XPS analysis discovered the increase in -C-O-, -C-N-, -N-H-, and -N=O- bonds at the surface of EstS1-treated PET film, indicating effective degradation. Consequently, this comprehensive kinetic, structural, and morphology-based analysis of the PET-degrading potential of EstS1 esterase encourages further enzyme engineering studies to exploit the dual potential of EstS1 esterase to degrade both plastic and plasticizers.

biophysics↗

bioRxiv2025

Unveiling the structural insights of PFAS-β-lactoglobulin binding mechanism mediating neuronal toxicity in neonates.

The strong, polar-covalent nature of C-F bonds contributes to the forever nature of per- and polyfluoroalkyl (PFAS) substances. PFAS are toxic to humans. Here, we have examined the ability of the small, globular, milk protein {beta}-lactoglobulin to bind PFAS. The protein transports hydrophobic and amphiphilic compounds, including retinol and fatty acids, for vision and brain development; therefore, underscoring its interactions with PFAS is significant. The crystal structures of {beta}-lactoglobulin complexed with PFOA (Perfluorooctanoic acid) at 2.0 ([A]), PFOS (Perfluorooctanesulfonic acid) at 2.5 ([A]), and PFDA (Perfluorodecanoic acid) at 2.0 ([A]) reveal high affinity of the compounds for the central calyx of {beta}-lactoglobulin, which is the canonical retinol and fatty acid binding site. Analyses of the data indicate significant hydrophobic interactions stabilizing the binding of the PFAS hydrophobic "tails" within the calyx and interactions between Lys60 and Lys69 and PFAS polar head groups. Comparative structural analysis revealed the presence of an open conformation of the EF loop containing the Glu89 latch residue in the complexed structures vis-a-vis the apo-form. Molecular dynamics (MD) simulations revealed high stability of the PFAS binding and attainment of energy minima in all complexes. The average binding energy of PFDA in {beta}-lactoglobulin calyx was -25 kcal/mol, which was higher than PFOS (-21 kcal/mol) and PFOA (-23 kcal/mol) due to increased van der Waals interactions of the longer hydrophobic chain of PFDA with {beta}-lactoglobulin. This work advances a mechanism by which {beta}-lactoglobulin can recruit PFAS and act as a transporter for the "forever" chemical, potentially mediating its neurotoxicity.

biophysics↗

bioRxiv2025

Integrative Transcriptomic Analysis Identifies Novel Mitochondrial Gene Targets in Parkinson's Disease.

Parkinsons disease (PD) involves the progressive loss of dopaminergic (DA) neurons within the substantia nigra (SN) region of the midbrain, although the precise molecular processes driving this degeneration are still not fully understood. This research investigates the expression patterns of genes associated with mitochondrial function in the SN and DA neurons of individuals with PD, aiming to uncover new potential therapeutic targets. Two independent RNA sequencing datasets, GSE7621 and GSE8397 (GPL-96), retrieved from the GEO database, were analyzed to identify mitochondria-related genes that are differentially expressed in the SN of PD patients. Gene Ontology and pathway enrichment analyses were also performed to gain insight into the molecular mechanisms involved. To validate our findings, we utilized an additional dataset, GSE49036. We also examined the altered expression of these mitochondrial-related genes in DA neurons using RNA-seq data from GSE169755, which includes DA neurons isolated from the SN of both PD patients and healthy controls. Finally, the proposed hypothesis was tested experimentally using an in vitro model of PD. This integrative analysis across multiple datasets reveals previously unrecognized mitochondrial gene candidates implicated in PD pathogenesis and highlights their potential as targets for therapeutic intervention.

neuroscience↗

bioRxiv2024

Unveiling Mechanistic and Structural Insights of EstS1 Esterase: A Potent Broad-Spectrum Phthalate Diester Degrading Enzyme

The ubiquitous presence of plastics and plasticizers around the globe has raised an alarming condition. Phthalate diesters are high-priority pollutants that mimic natural hormones and act as endocrine disruptors upon entering living systems. While certain bacterial esterases have been identified for their role in phthalate diester degradation, their structural and mechanistic characteristics remain largely unexplored. A thermostable and pH-tolerant EstS1 esterase from Sulfobacillus acidophilus catalyzes the conversion of low molecular weight phthalate diesters to monoesters. This study highlights the unique potential of EstS1 to degrade high molecular weight bis(2-ethylhexyl) phthalate (DEHP) by employing biophysical and biochemical approaches along with in-depth structural analysis utilizing high-resolution crystal structures in both apo and complex forms, with various substrates, products, and their analogs to elucidate mechanistic details. The catalytic tunnel mediating entry and exit of the substrate and product, respectively, centralized the Ser-His-Asp triad performing catalysis by bi-bi ping-pong mechanism, forming a tetrahedral intermediate. Additionally, structural analysis of the polypropylene analog jeffamine with EstS1 revealed effective covalent binding, demonstrating its multifunctional capability. Mutation analysis showed that the Met207Ala mutation abolished DEHP binding at the active site, confirming its essential role in supporting catalysis. These findings underscore the potential of EstS1 as a key tool for advancing technologies aimed at phthalate diesters biodegradation.

biophysics↗

bioRxiv2024

Unveiling the genes and pathways that are dysregulated in dopaminergic neurons during both familial and sporadic Parkinson's disease.

Parkinsons disease (PD), a neurodegenerative disorder characterized by dopaminergic (DA) neuron loss in the substantia nigra, manifests as familial (genetically linked) or idiopathic (sporadic) forms. Despite distinct etiologies, both subtypes converge on shared pathological mechanisms that remain poorly understood. This study focused on identifying "hub genes" that might drive DA neuron degeneration in familial and idiopathic PD. The gene expression data from three publicly available datasets were reanalyzed. These datasets included samples from DA neurons derived from postmortem brains and patient-derived induced pluripotent stem cells. Twelve hub genes were identified to be dysregulated across all three datasets. The hub genes were found to play vital roles in membrane trafficking and vesicle-mediated transport. NetworkAnalyst-based reconstruction linked these hub genes to various other diseases. Experimental validation in neurotoxin-induced SH-SY5Y cell models of PD confirmed significant changes in the mRNA levels of some of the hub genes. Crucially, silencing one of the hub genes in Caenorhabditis elegans promoted DA neuron degeneration. Our study identifies potential candidates as therapeutic targets for DA neuron degeneration in familial and idiopathic PD.

neuroscience↗