Singh Ankit Satyaprakash
Banaras Hindu University, IndiaPresentation Title:
Combinatorial model of traumatic brain injury and Parkinson’s disease: Investigating alpha-synuclein acetylation and its role in proteasome dysfunction, apoptosis, and neuroinflammation
Abstract
Introduction:
Traumatic brain injury (TBI) and Parkinson’s disease (PD) are debilitating neurological disorders that severely impact quality of life. Emerging evidence suggests a link between repetitive mild traumatic brain injury (rmTBI) and the onset or acceleration of PD. A key factor in this connection is alpha-synuclein (αsyn), a protein closely associated with PD pathology. This study focuses on how the acetylation of α-syn influences neurodegenerative processes triggered by rmTBI.
Objective:
The aim of this research is to develop a combinatorial rodent model to investigate the effects of rmTBI on PD progression, with a particular focus on the role of α-syn acetylation in neuroinflammation and proteasome dysfunction.
Methodology:
Swiss albino mice were subjected to 30 days of rmTBI to simulate brain trauma, followed by administration of MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) to induce PD-like symptoms. The mice were divided into three groups: Sham (no intervention), PD-only (MPTP treatment), and TBI + PD (rmTBI followed by MPTP). Molecular techniques, including Western blotting, immunohistochemistry, high-resolution mass spectrometry, RNA sequencing, and RT-PCR, were used to investigate acetylated proteins in brain tissue.
Results:
The TBI + PD group exhibited a significant increase in α-syn acetylation compared to both the PD-only and Sham groups. Furthermore, this group demonstrated proteasome dysfunction, elevated markers of apoptosis, and heightened neuroinflammatory responses. RNA sequencing revealed upregulation of genes associated with neuroinflammation and stress.
Conclusion:
The findings suggest that α-syn acetylation plays a critical role in neurodegeneration, especially when TBI precedes PD. This study highlights potential therapeutic targets for PD in individuals with a history of TBI by identifying molecular mechanisms that drive neuroinflammation and proteasome dysfunction.
Biography
Singh Ankit Satyaprakash is a researcher in the Department of Biochemistry, Institute of Science, Banaras Hindu University (BHU), Uttar Pradesh, India, under the mentorship of Professor Surya Pratap Singh. His research is centered on uncovering the molecular mechanisms that connect traumatic brain injury (TBI) and Parkinson’s disease (PD), with a special focus on the role of alphasynuclein acetylation in proteasome dysfunction and neuroinflammation. At this international conference, Singh will present his work on developing a combinatorial rodent model to study the progression of PD following repetitive mild traumatic brain injury (rmTBI). His research employs advanced molecular techniques such as high-resolution mass spectrometry, RNA sequencing, and immunohistochemistry to investigate changes in acetylated proteins and identify potential therapeutic targets for neurodegenerative disorders. By integrating cutting-edge biochemical methodologies, Singh's work aims to shed light on the mechanisms that drive neurodegeneration in individuals with a history of brain trauma, providing critical insights into potential interventions for PD.