Combinatorial Treatment Effects in a Cell Culture Model of Alzheimer's Disease
| Autor: | Charles Saunders, Ewa A. Bienkiewicz, James Olcese, Stephen Beesley |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Disease Resveratrol Bioinformatics Transfection Catechin 03 medical and health sciences chemistry.chemical_compound Therapeutic approach Amyloid beta-Protein Precursor Mice Neuroblastoma 0302 clinical medicine Cell Line Tumor Stilbenes Medicine Dementia Animals Humans Melatonin chemistry.chemical_classification Reactive oxygen species Amyloid beta-Peptides business.industry General Neuroscience Cellular pathways General Medicine medicine.disease Peptide Fragments Gene Expression Regulation Neoplastic Psychiatry and Mental health Clinical Psychology Drug Combinations 030104 developmental biology chemistry Proto-Oncogene Proteins c-bcl-2 Cell culture Mutation Cytokines Geriatrics and Gerontology Cell culture model business Reactive Oxygen Species 030217 neurology & neurosurgery Antipsychotic Agents |
| Zdroj: | Journal of Alzheimer's disease : JAD. 55(3) |
| ISSN: | 1875-8908 |
| Popis: | Background Alzheimer's disease (AD) is the leading cause of dementia, and as its prevalence increases, so does its detrimental impact on society. The currently available therapies have limited efficacy, leaving AD patients on an irrevocably fatal path of this disease. Objective The purpose of this study was to test efficacy of a novel combinatorial treatment approach to alleviate AD-like pathology. Methods We selected four naturally occurring compounds and used them in different combinations to test their effect on AD-like pathology. Employing a well-established cell culture AD model system, we evaluated levels of several diverse biomarkers associated with a number of cellular pathways associated with AD. The readouts included: amyloid-β peptides, anti-inflammatory and anti-apoptotic proteins, oxidative enzymes, and reactive oxygen species. Results Using this approach, we demonstrated that the compounds delivered in combination had higher efficacy than individual treatments. Specifically, we observed significant reduction in levels of the amyloid-β peptides, as well as pro-inflammatory proteins and reactive oxygen species. Similarly, delivery of compounds in combination resulted in an increased expression of anti-apoptotic proteins and anti-oxidative enzymes. Collectively, these modifications in AD pathology biomarkers reflect a promising therapeutic and preventive strategy to combat this disease. Conclusion The above findings support a novel therapeutic approach to address a currently unmet medical need, which would benefit not only AD patients and their caregivers, but also society as a whole. |
| Databáze: | OpenAIRE |
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