Flavonoids: The Innocuous Agents Offering Protection against Alzheimer's Disease Through Modulation of Proinflammatory and Apoptotic Pathways.

Abstract

Beginning from mild cognitive impairment in patients suffering from Alzheimer's disease (AD), dementia sets in with the progress of the disease. The pathological changes in the brain begin fifteen to twenty years before AD related dementia develops. Presence of senile plaques and neurofibrillary tangles are considered the hallmarks of AD brain. Chronic inflammation resulting from the disruption of the equilibrium between anti-inflammatory and pro-inflammatory signalling emerges as another important feature of AD and also other neurodegenerative diseases. Substantial studies demonstrate that this sustained immune response in the brain is associated with neuronal loss, along with facilitation and aggravation of Aβ and NFT pathologies. Although it is well accepted that neuroinflammation and oxidative stress have both detrimental and beneficial influences on the brain tissues, the involvement of microglia and astrocytes in the onset and progress of the neurodegenerative process in AD is becoming increasingly recognized. Although the cause of neuronal loss is known to be apoptosis, the mechanism of promotion of neuronal death remains undisclosed. Controlling the activation of the resident immune cells and/or the excessive production of pro-inflammatory and pro-oxidant factors could be effective as therapeutics. Among the phytonutrients, the neuroprotective role of flavonoids is beyond doubt. This review is an exploration of the literature on the role of flavonoids in these aspects. Flavonoids are not only effective in ameliorating the adverse consequences of oxidative stress but also impede the development of late onset Alzheimer's disease by modulating affected signalling pathways and boosting signalling crosstalk.