*Microglial activation triggers inflammatory cascades in the brain, resulting in demyelination and white matter lesions, often accompanied by enlarged ventricles and small vessel disease.
*AGEs were first described by Louis-Camille Maillard in 1912.
*AGEs can affect nearly every cell type and molecule in the body by acting either directly or indirectly through binding to specific receptors.
*Increased levels of AGEs along with high tissue expression of their signal transduction receptor, RAGE, can initiate and exacerbate diverse pathological conditions by enhancing the transcription of genes associated with pro-inflammatory mediators and in turn, by promoting abnormal protein synthesis.
*AGE-RAGE interaction triggers oxidative stress, disrupting the delicate equilibrium of ROS in the brain microenvironment.
*This oxidative milieu fosters a chronic state of inflammation, evidenced by the activation of glial cells, thus perpetuating the cycle of neuronal damage.
*High ROS levels instigate synaptic dysfunction, impairing inter-neuronal communication and compromising cognitive function.
*Autophagy, the clearance process of dysfunctional proteins from the cells, is also impaired by the AGE-RAGE pathway, contributing to the accumulation of toxic protein compounds in neurons.
*AGEs have been directly implicated in the pathogenesis of both AD and PD, by contributing to the neurodegenerative processes characteristic of these disorders.
*Lifestyle modifications, small molecule inhibitors or monoclonal antibodies targeting RAGE have been proposed to block AGE-RAGE interactions and downstream signaling pathways.
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