Cross-talk between oxidative stress and modifications of cholinergic and glutaminergic receptors in the pathogenesis of Alzheimer's disease¹

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its pathogenesis is likely to be associated with multiple etiologies and mechanisms in which oxidative stress and deficits of neurotransmitter receptors may play important roles. It has been indicated that a high level of free radicals can influence the expressions of nicotinic receptors (nAChRs), muscarinic receptors (mAChRs), and N-methyl-D-aspartate (NMDA) receptors, exhibiting disturbances of cellular membrane by lipid peroxidation, damages of the protein receptors by protein oxidation, and possible modified gene expressions of these receptors by DNA oxidation. nAChRs have shown an antioxidative effect by a direct or an indirect pathway; mAChR stimulation may generate reactive oxygen species, which might be a physiological compensative reaction, or improve oxidative stress; and high stimulation to NMDA receptors can increase the sensitivity of oxidative stress of neurons. This review may provide complemental information for understanding the correlation between oxidative stress and changed cholinergic and glutaminergic receptors in AD processing, and for revealing the underlying molecular mechanisms of these factors in the multiple etiologies and pathophysiology of the disorder.

Brain Region-Specific Changes in Oxidative Stress and Neurotrophin Levels in Autism Spectrum Disorders (ASD)

“…Brain region-selective sensitivity to the toxins may be determined by specific neuronal populations. Both the dopaminergic neurons [30] and the cholinergic neurons are particularly sensitive to oxidative stress [31]. Thus brain regions primarily relying on cholinergic transmission, such as the hippocampus and inhibitory neurons of the substantia nigra may be especially affected by oxidative stress.…”

Baicalin attenuates oxygen-glucose deprivation-induced injury by inhibiting oxidative stress-mediated 5-lipoxygenase activation in PC12 cells

“…Therefore, in addition to inhibiting 5-LOX activation induced by the elevated intracellular Ca 2+ via NMDA receptor activation [13] , baicalin also inhibits 5-LOX activation via the ROS/p38 MAPK pathway. In addition, there is crosstalk between NMDA-induced excitotoxicity and oxidative stress [29,30] , and baicalin inhibits 5-LOX activation after NMDA receptor-mediated excitotoxicity [13] . Whether baicalin affects a common pathway of 5-LOX activation in both pathological processes requires further investigation.…”

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

“…Studies have demonstrated that oxidative imbalance is a manifestation of AD that even precedes Aβ deposition and NFTs formation, and plays a crucial role in neuronal degeneration [5,6] . Increased oxidative stress (OS) has been implicated in the aging process and is a result of the imbalance between the generation and clearance of reactive oxygen species (ROS).…”