Alzheimer’s disease (AD) is a complex, neurodegenerative disorder that is characterized by the presence of neuronal loss, amyloid plaques, and neurofibrillary tangles (NFTs) in the brain. The abnormal production of the beta-Amyloid protein (A-beta) results in the formation of plaques and is believed to promote the hyperphosphorylation of intracellular Tau and the formation of NFTs. These pathophysiological effects are thought to cause synapse loss and neuronal death. Recently, researchers have suggested that chronic neuroinflammation plays an important role in the pathogenesis of AD. It has been shown that A-beta deposits initiate a neuroinflammatory response by activating microglia and astrocytes and promoting the release of inflammatory mediators such as cytokines and chemokines. In addition, this inflammatory response may hinder activated microglia from phagocytizing A-beta, causing the peptide to accumulate and thus aggregate into amyloid plaques, which then further promotes glial cell activation and cytokine secretion. Chronically activated microglia can damage adjacent neurons by releasing highly toxic products such as reactive oxygen and nitrogen species. Additionally, chronic neuroinflammation can trigger the breakdown of the blood-brain barrier, which contributes to increased migration of peripheral immune cells into the central nervous system and, possibly, increased risk of developing AD. By elucidating the contribution of proinflammatory mediators to the progression of AD, novel therapeutic targets for this devastating neurological disorder may be identified.
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