مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Integrating Monoclonal Antibody Therapy with Complementary Medicine: A Bioinformatic and Chemoinformatic Deep Dive into Gene and Compound Networks in Alzheimer’s Disease
Integrating Monoclonal Antibody Therapy with Complementary Medicine: A Bioinformatic and Chemoinformatic Deep Dive into Gene and Compound Networks in Alzheimer’s Disease
Rezvan Hosseiny,1Neda Ghanbari,2Fatemeh Hajibabaie,3Navid Abedpoor,4,*
1. Department of Biotechnology, Fal.C., Islamic Azad University, Isfahan, Iran 2. Department of Genetics, Fal.C., Islamic Azad University, Isfahan, Iran 3. Department of Biology, ShK.C., Islamic Azad University, ShahreKord, Iran. 4. Department of Sports Physiology, Isf.C., Islamic Azad University, Isfahan, Iran.
Introduction: Alzheimer’s disease is a progressive neurodegenerative disorder and the primary cause of dementia worldwide, leading to a decline in memory, thinking skills, and independent functioning. Its hallmark pathology includes the accumulation of amyloid-beta plaques and tau tangles in the brain, driving neuronal damage and cognitive impairment. The challenge of Alzheimer’s is compounded by its intricate genetic, molecular, and environmental risk factors, with current therapies offering only partial symptomatic relief. Recent breakthroughs have introduced monoclonal antibody therapies—lecanemab and donanemab—which selectively target and clear amyloid-beta aggregates, marking a paradigm shift towards disease modification for early-stage Alzheimer’s. However, despite promising efficacy, these biologic drugs do not address all aspects of disease progression or the underlying multifactorial biology. Complementary medicine—including herbal compounds, mind-body practices, and lifestyle interventions—offers a holistic approach, aiming to mitigate oxidative stress, neuroinflammation, and other non-amyloid pathways involved in Alzheimer’s. Integrative strategies that combine pharmaceutical advances with complementary practices may enhance neuroprotection, cognitive function, and overall patient well-being. This provides the backdrop for exploring Alzheimer's treatments that combine multiple approaches, like cutting-edge antibody treatments alongside proven complementary therapies, to enhance patient well-being.
Our goal is to identify molecular signatures and therapeutic synergies between lecanemab, donanemab, and polyherbal complementary medicine. We achieved this by integrating bioinformatics and cheminformatics analyses of sex-specific Alzheimer’s gene profiles with compound docking affinity.
Methods: Transcriptomics datasets for male and female Alzheimer’s patients were analysed for differential gene expression (P < 0.01). Network modelling identified 12 hub genes (notably EGFR) critical in disease pathogenesis. Molecular docking and pharmacophore modeling evaluated the binding affinities of 22 bioactive compounds from 14 medicinal plants to hub proteins, focusing on neuroprotective, antioxidant, and anti-inflammatory potential.
Results: Analysis revealed 1,489 female-specific and 851 male-specific Alzheimer’s genes with significant dysregulation. Physical training modulated 13,985 genes (272 upregulated, 1,069 downregulated; P < 0.001), restoring key expression profiles. Venn analysis confirmed 35 overlapping genes among sexes and physical activity. EGFR and 11 other hub proteins showed prominent centrality in the disease network. Docking studies found fisetin, quercetin, curcumin, gingerol, and nobiletin possessed strong binding affinity for EGFR, supporting a biological rationale for their senolytic and cognitive-protective effects.
Conclusion: Bioinformatic and chemoinformatic approaches pinpoint key sex- and activity-dependent Alzheimer’s genes and validate high-affinity herbal ligands for protein modulation. Combining monoclonal antibody therapies with targeted complementary medicine and regular training emerges as a promising integrative strategy to reverse molecular hallmarks and enhance quality of life in Alzheimer’s patients.