Biology subjects

Kharbanda, N.

Publications and source records attributed to Kharbanda, N..

3 recordsLinked to original sources

bioRxiv2026

Ferroptosis links α-synuclein pathology across brain and skeletal muscle in Parkinsons disease

Parkinsons disease (PD) is increasingly recognized as a multisystem disorder, yet the mechanisms linking neurodegeneration with muscle dysfunction remain largely unknown. In this study, using an A53T -synuclein (Syn) transgenic mouse model, we demonstrate coordinated pathological changes across the brain-muscle organs characterized by systemic inflammation, iron accumulation, oxidative stress, and ferroptosis-associated lipid peroxidation. Our quantitative proteomics data revealed dysregulated iron metabolism and ferroptosis in the brain and skeletal muscle. Biochemical validation confirmed increased expression of Transferrin receptor 1 (TFRC), elevated lipid peroxidation, and suppression of antioxidant defenses, including SLC7A11 and GPX4, indicating enhanced ferroptotic susceptibility. Cell-surface proteomics and biophysical assays further revealed that pathological Syn directly interacts with TFRC, promoting iron accumulation and ferroptosis-associated oxidative damage in neuronal and muscle cells. Together, our findings identify ferroptosis as a shared pathological mechanism across the brain and muscle, mediated by the Syn-TFRC interaction, thus linking neurodegeneration and peripheral muscle pathology in PD.

neuroscience↗

bioRxiv2025

Synapse-related protein alterations and estradiol deficiency associate with early Parkinsonism in female A53T-α-synuclein transgenic mice fed on a high-fat diet

Substantial evidence highlights the detrimental impact of a fat-rich diet on cognitive and emotional behaviour. Epidemiological studies have linked the consumption of saturated fat with an increased risk of Parkinsons disease (PD), whereas a low-fat or ketogenic diet is reported to improve both motor and non-motor symptoms. Several animal model studies further support these associations. However, the impact of a high-fat diet (HFD) on sex-specific behavioural alterations and the underlying molecular mechanism in PD remains poorly studied. In the present study, we investigated the impact of HFD on PD progression in a sex-specific manner using the A53T transgenic mouse model of PD. Behavioural and pathophysiological analyses revealed a faster onset and progression of PD-like phenotype in female mice exposed to HFD compared with the male mice. Proteomics profiling of brain tissues demonstrated positive enrichment of immune system-related pathways in males, while females exhibited considerable downregulation of synapse-associated pathways under HFD conditions. The reduced estradiol level was identified as a potential factor contributing to synaptic dysfunction and the subsequent early onset of PD in female mice. These findings provide novel insights into the sex-specific consequences of HFD on PD pathogenesis and highlight the role of estrogen-linked synaptic vulnerability in mediating diet-induced PD onset.

neuroscience↗

bioRxiv2024

Arabidopsis AtGELP53 modulates polysaccharide acetylation and defense response through oligosaccharide-mediated signaling

O-acetylation is a crucial substitution found in hemicelluloses and pectin which are necessary for maintaining the flexibility and structural integrity of the cell. A balanced polysaccharide O-acetylation level is maintained by cell wall acetyl transferases and esterases present in different cell organelles. Specifically, the role of esterases in cell wall acetylation metabolism is less explored. Therefore, we investigated the role of AtGELP53 from the GELP family of esterases or lipases. Here, we show that AtGELP53 is localized in the plasma membrane. Analysis of AtGELP53 overexpressing independent transgenic lines revealed a decrease in xyloglucan acetylation, changes in other polysaccharide acetylation and alteration in cell wall composition. The series of elicitor-based, transcriptomic and proteomic analyses in AtGELP53 overexpressing lines suggested that oligosaccharide-mediated signalling activates the cell wall and defence-related genes primarily because of xyloglucan deacetylation. Furthermore, AtGELP53 overexpression plants showed resistance against Pseudomonas syringae and Ralstonia solanacearum through activation of elicitor-mediated defense response. Overall, our findings outline the role of AtGELP53 in polysaccharide acetylation, cell wall remodelling and defense through the activation of plant cell wall integrity.

plant biology↗