ABSTRACT
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and symptoms develop gradually over many years. The current direction for medication development in AD is focused on neuro-inflammation and oxidative stress. Amyloid-ß (Aß) deposition activates microglia leading to neuro-inflammation and neurodegeneration induced by activation of COX-2 via NFκB p50 in glioblastoma cells. Objective: The study aimed to evaluate the concentration of COX-2 and NFκB p50 in serum of AD, mild cognitive impairment (MCI), and geriatric control (GC) and to establish a blood-based biomarker for early diagnosis and its therapeutic implications. Methods: Proteins and their mRNA level in blood of study groups were measured by surface plasmon resonance (SPR) and quantitative polymerase chain reaction (qPCR), respectively. The level of protein was further validated by western blot. The binding study of designed peptide against COX-2 by molecular docking was verified by SPR. The rescue of neurotoxicity by peptide was also checked by MTT assay on SH-SY5Y cells (neuroblastoma cell line). Results: Proteins and mRNA were highly expressed in AD and MCI compared to GC. However, COX-2 decreases with disease duration. The peptide showed binding affinity with COX-2 with low dissociation constant in SPR and rescued the neurotoxicity of SH-SY5Y cells by decreasing the level of Aß, tau, and pTau proteins. Conclusions: It can be concluded that COX-2 protein can serve as a potential blood-based biomarker for early detection and can be a good platform for therapeutic intervention for AD.
Subject(s)
Alzheimer Disease , Neuroblastoma , Neurodegenerative Diseases , Humans , Aged , Alzheimer Disease/genetics , Cyclooxygenase 2 , Molecular Docking Simulation , Amyloid beta-Peptides/metabolism , Inflammation/metabolism , Biomarkers , Early Diagnosis , RNA, Messenger , tau Proteins/metabolism , Peptide Fragments/therapeutic useABSTRACT
Background: This review analyzed the magnitude of the COVID-19 pandemic globally and in India and the measures to counter its effect using natural and innate immune booster molecules. The study focuses on two phases: the first focuses on the magnitude, and the second on the effect of antioxidants (natural compounds) on SARS-CoV-2. Methods: The magnitude of the prevalence, mortality, and comorbidities was acquired from the World Health Organization (WHO) report, media, a report from the Ministry of Health and Family Welfare (MoHFW), newspapers, and the National Centre of Disease Control (NCDC). Research articles from PubMed as well as other sites/journals and databases were accessed to gather literature on the effect of antioxidants. Results: In the elderly and any chronic diseases, the declined level of antioxidant molecules enhanced the reactive oxygen species, which in turn deprived the immune system. Conclusion: Innate antioxidant proteins like sirtuin and sestrin play a vital role in enhancing immunity. Herbal products and holistic approaches can also be alternative solutions for everyday life to boost the immune system by improving the redox balance in COVID-19 attack. This review analyzed the counteractive effect of alternative therapy to boost the immune system against the magnitude of the COVID-19 pandemic.
