Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease

Bioinformatics has become an essential field of interest for examining intricate biological data and revealing the possible mechanisms that have significant contribution to various diseases. The field encompasses diverse applications, such as genomic, transcriptomic, proteomic, and network analysis,...

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Main Authors: Kirti Bamel, Anil Panwar, Mukesh Kumar, Sunil Kumar, Varruchi Sharma, Anil Sharma
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Brain Disorders
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666459325000526
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author Kirti Bamel
Anil Panwar
Mukesh Kumar
Sunil Kumar
Varruchi Sharma
Anil Sharma
author_facet Kirti Bamel
Anil Panwar
Mukesh Kumar
Sunil Kumar
Varruchi Sharma
Anil Sharma
author_sort Kirti Bamel
collection DOAJ
description Bioinformatics has become an essential field of interest for examining intricate biological data and revealing the possible mechanisms that have significant contribution to various diseases. The field encompasses diverse applications, such as genomic, transcriptomic, proteomic, and network analysis, which hold significant promise for uncovering critical pathways and molecules implicated in the TBI-AD mechanism. Numerous studies have indicated that bioinformatics has yielded significant insights into inflammation, immune response, tau pathology, amyloid-β pathology, and changes in neuroplasticity following TBI, potentially contributing to the onset of AD. Building on this, systems biology approaches are essential for integrating multi-omics data, which aids in the discovery of biomarkers, drug targets, and treatment strategies. Recent advancements in high-throughput and high-content screens (HCS) for neurodegenerative diseases have primarily focused on inherited neurodegenerative disorders. Traumatic brain injury (TBI) is increasingly recognized as a major risk factor for the development of neurodegenerative diseases (NDDs), particularly Alzheimer’s disease (AD). The molecular and cellular responses triggered by TBI–such as oxidative stress, mechanical deformation, and excitotoxicity—disrupt critical homeostatic processes, including axonal transport, protein folding, and clearance. These disruptions contribute to hallmark AD pathologies, including amyloid-beta (Aβ) plaque deposition and tau hyperphosphorylation leading to neurofibrillary tangle formation. Furthermore, neuroinflammatory responses and the overproduction of reactive oxygen species (ROS) exacerbate neuronal injury and accelerate neurodegenerative progression. Advances in bioinformatics, particularly through high-throughput omics analyses, have illuminated differentially expressed genes (DEGs), dysregulated pathways, and key molecular players involved in these processes. These insights are guiding the development of targeted therapeutic strategies, including NMDAR modulators to alleviate excitotoxicity, beta-secretase inhibitors to limit Aβ aggregation, and anti-inflammatory agents aimed at suppressing COX2-mediated inflammation. By integrating findings from clinical data and preclinical models, bioinformatics continues to deepen our understanding of the complex interplay between TBI and AD. Ultimately, this integrative approach is essential for identifying early diagnostic markers, optimizing treatment strategies, and improving long-term outcomes for individuals affected by TBI-induced neurodegeneration.
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spelling doaj-art-c7c03f0cacee49429b62938b71b9cd622025-08-20T03:26:20ZengElsevierBrain Disorders2666-45932025-06-011810023210.1016/j.dscb.2025.100232Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s diseaseKirti Bamel0Anil Panwar1Mukesh Kumar2Sunil Kumar3Varruchi Sharma4Anil Sharma5Department of Bioinformatics and Computational Biology, CCS Haryana Agricultural University, Hisar 125004, IndiaDepartment of Bioinformatics and Computational Biology, CCS Haryana Agricultural University, Hisar 125004, India; Corressponding author.Department of Biotechnology, Ambala College of Engineering and Applied Research, Mithapur, Ambala, Haryana 133101, IndiaDepartment of Botany, CRM Jat College, Hisar 125001, IndiaDepartment of Biotechnology, Sri Guru Gobind Singh College, Chandigarh 160001, IndiaDepartment of Biotechnology, Amity University, Mohali 140306, IndiaBioinformatics has become an essential field of interest for examining intricate biological data and revealing the possible mechanisms that have significant contribution to various diseases. The field encompasses diverse applications, such as genomic, transcriptomic, proteomic, and network analysis, which hold significant promise for uncovering critical pathways and molecules implicated in the TBI-AD mechanism. Numerous studies have indicated that bioinformatics has yielded significant insights into inflammation, immune response, tau pathology, amyloid-β pathology, and changes in neuroplasticity following TBI, potentially contributing to the onset of AD. Building on this, systems biology approaches are essential for integrating multi-omics data, which aids in the discovery of biomarkers, drug targets, and treatment strategies. Recent advancements in high-throughput and high-content screens (HCS) for neurodegenerative diseases have primarily focused on inherited neurodegenerative disorders. Traumatic brain injury (TBI) is increasingly recognized as a major risk factor for the development of neurodegenerative diseases (NDDs), particularly Alzheimer’s disease (AD). The molecular and cellular responses triggered by TBI–such as oxidative stress, mechanical deformation, and excitotoxicity—disrupt critical homeostatic processes, including axonal transport, protein folding, and clearance. These disruptions contribute to hallmark AD pathologies, including amyloid-beta (Aβ) plaque deposition and tau hyperphosphorylation leading to neurofibrillary tangle formation. Furthermore, neuroinflammatory responses and the overproduction of reactive oxygen species (ROS) exacerbate neuronal injury and accelerate neurodegenerative progression. Advances in bioinformatics, particularly through high-throughput omics analyses, have illuminated differentially expressed genes (DEGs), dysregulated pathways, and key molecular players involved in these processes. These insights are guiding the development of targeted therapeutic strategies, including NMDAR modulators to alleviate excitotoxicity, beta-secretase inhibitors to limit Aβ aggregation, and anti-inflammatory agents aimed at suppressing COX2-mediated inflammation. By integrating findings from clinical data and preclinical models, bioinformatics continues to deepen our understanding of the complex interplay between TBI and AD. Ultimately, this integrative approach is essential for identifying early diagnostic markers, optimizing treatment strategies, and improving long-term outcomes for individuals affected by TBI-induced neurodegeneration.http://www.sciencedirect.com/science/article/pii/S2666459325000526Traumatic brain injury (TBI)Amyloidogenic processesAmyloid-beta (Aβ) plaquesTau neurofibrillary tanglesNeurofilament proteinsNeuronal deformation
spellingShingle Kirti Bamel
Anil Panwar
Mukesh Kumar
Sunil Kumar
Varruchi Sharma
Anil Sharma
Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease
Brain Disorders
Traumatic brain injury (TBI)
Amyloidogenic processes
Amyloid-beta (Aβ) plaques
Tau neurofibrillary tangles
Neurofilament proteins
Neuronal deformation
title Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease
title_full Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease
title_fullStr Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease
title_full_unstemmed Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease
title_short Traumatic brain injury as a precursor to neurodegenerative diseases: Mechanisms linking TBI to Alzheimer’s disease
title_sort traumatic brain injury as a precursor to neurodegenerative diseases mechanisms linking tbi to alzheimer s disease
topic Traumatic brain injury (TBI)
Amyloidogenic processes
Amyloid-beta (Aβ) plaques
Tau neurofibrillary tangles
Neurofilament proteins
Neuronal deformation
url http://www.sciencedirect.com/science/article/pii/S2666459325000526
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