RESUMEN
Alzheimer's disease (AD) is a chronic, neurodegenerative brain disorder affecting millions of Americans that is expected to increase in incidence with the expanding aging population. Symptomatic AD patients show cognitive decline and often develop neuropsychiatric symptoms due to the accumulation of insoluble proteins that produce plaques and tangles seen in the brain at autopsy. Unexpectedly, some clinically normal individuals also show AD pathology in the brain at autopsy (asymptomatic AD, AsymAD). In this study, SWItchMiner software was used to identify key switch genes in the brain's entorhinal cortex that lead to the development of AD or disease resilience. Seventy-two switch genes were identified that are differentially expressed in AD patients compared to healthy controls. These genes are involved in inflammation, platelet activation, and phospholipase D and estrogen signaling. Peroxisome proliferator-activated receptor γ (PPARG), zinc-finger transcription factor (YY1), sterol regulatory element-binding transcription factor 2 (SREBF2), and early growth response 1 (EGR1) were identified as transcription factors that potentially regulate switch genes in AD. Comparing AD patients to AsymAD individuals revealed 51 switch genes; PPARG as a potential regulator of these genes, and platelet activation and phospholipase D as critical signaling pathways. Chemical-protein interaction analysis revealed that valproic acid is a therapeutic agent that could prevent AD from progressing.
Asunto(s)
Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Genes de Cambio/genética , Inflamación/genética , Envejecimiento/genética , Envejecimiento/patología , Enfermedad de Alzheimer/patología , Encéfalo/metabolismo , Encéfalo/patología , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Corteza Entorrinal/patología , Regulación de la Expresión Génica/genética , Humanos , Inflamación/patología , PPAR gamma/genética , Fosfolipasa D/genética , Placa Amiloide , Transducción de Señal/genética , Programas Informáticos , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Factor de Transcripción YY1/genéticaRESUMEN
BACKGROUND: The Mediterranean diet, which is rich in olive oil, nuts, and fish, is considered healthy and may reduce the risk of chronic diseases. METHODS: Here, we compared the transcriptome from the blood of subjects with diets supplemented with olives, nuts, or long-chain omega-3 fatty acids and identified the genes differentially expressed. The dietary genes obtained were subjected to network analysis to determine the main pathways, as well as the transcription factors and microRNA interaction network to elucidate their regulation. Finally, a gene-associated disease interaction network was performed. RESULTS: We identified several genes whose expression is altered after the intake of components of the Mediterranean diets compared to controls. These genes were associated with infection and inflammation. Transcription factors and miRNAs were identified as potential regulators of the dietary genes. Interestingly, caspase 1 and sialophorin are differentially expressed in the opposite direction after the intake of supplements compared to Alzheimer's disease patients. In addition, ten transcription factors were identified that regulated gene expression in supplemented diets, mild cognitive impairment, and Alzheimer's disease. CONCLUSIONS: We determine genes whose expression is altered after the intake of the supplements as well as the transcription factors and miRNA involved in their regulation. These genes are associated with schizophrenia, neoplasms, and rheumatic arthritis, suggesting that the Mediterranean diet may be beneficial in reducing these diseases. In addition, the results suggest that the Mediterranean diet may also be beneficial in reducing the risk of dementia.
Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Nueces , Olea , Enfermedad de Alzheimer , Disfunción Cognitiva , Dieta Mediterránea , Aceites de Pescado , MicroARNs/genética , Aceite de Oliva , Factores de Transcripción , TranscriptomaRESUMEN
Parkinson's disease (PD) is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction, and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline, and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.