The Natural Product Curcumin as a Potential Coadjuvant in Alzheimer’s Treatment
Authors: Morales, Inelia | Cerda-Troncoso, Cristóbal | Andrade, Víctor | Maccioni, Ricardo B.
Article Type: Research Article
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive cognitive impairment of patients, affecting around 12% of people older than 65 years old. WHO estimated that over 48.6 million all over the world suffer this disease. On the basis of cumulative results on our research, we have postulated the neuroimmunomodulation hypothesis that appears to provide a reasonable explanation of both the preclinical and clinical observations. In this context, the long-term activation of the innate immune system triggers an anomalous cascade of molecular signals, finally leading to tau oligomerization in the pathway to neuronal degeneration. In the present scenario …of the failure of many anti-AD drugs, nutraceutical compounds provide an avenue for AD prevention and possibly as coadjuvants in the treatment of this disease. Recent discoveries point to the relevance of curcumin, a natural anti-inflammatory agent, in controlling oxidative stress and improving cholinergic function in the brain, even though the mechanisms underlying these actions are unknown. We investigated the effects of curcumin in cultures of neuronal cells. For this study, we exposed cells to prooxidant conditions, both in the presence and absence of curcumin. Our data reveal that curcumin exert a strong neuroprotective effect in N2a cells, thus preventing toxicity by oxidative agents H2 O2 and Fe+3 . This is supported by results that indicate that curcumin control the neurodegenerative effects of both oxidative agents, relieving cells from the loss of neuritogenic processes induced by prooxidants. In addition, curcumin was able to slow down the tau aggregation curve and disassemble tau pathological oligomeric structures. Data suggest that curcumin could be a potential compound for prevention of cognitive disorders associated with AD. Show more
Keywords: Alzheimer’s disease, curcumin and derivatives, functional effects in neurons, prevention, treatment
DOI: 10.3233/JAD-170354
Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 451-460, 2017
Tau Oligomers and Fibrils Induce Activation of Microglial Cells
Authors: Morales, Inelia | Jiménez, José M. | Mancilla, Marcela | Maccioni, Ricardo B.
Article Type: Research Article
Abstract: Neuroinflammation is a process related to the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Increasing sets of evidence support the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration, a process we are calling neuroimmunomodulation in AD. On the basis of the hypothesis that pathological tau aggregates induce microglial activation with the subsequent events of the neuroinflammatory cascade, we have studied the effects of tau oligomeric species and filamentous structures over microglial cells in vitro. Tau oligomers and fibrils were induced by arachidonic acid and then their actions …assayed upon addition to microglial cells. We showed activation of the microglia, with significant morphological alterations as analyzed by immunofluorescence. The augmentation of nitrites and the proinflammatory cytokine IL-6 was evaluated in ELISA assays. Furthermore, conditioned media of stimulated microglia cells were exposed to hippocampal neurons generating altered patterns in these cells, including shortening of neuritic processes and cytoskeleton reorganization. Show more
Keywords: Alzheimer's disease, glial cells, neuroinflammation, tau aggregates
DOI: 10.3233/JAD-131843
Citation: Journal of Alzheimer's Disease, vol. 37, no. 4, pp. 849-856, 2013