Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease

Cognitive dysfunction is one of the most typical characteristics in various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (advanced stage). Although several mechanisms like neuronal apoptosis and inflammatory responses have been recognized to be involved in the pathogenesis of cognitive dysfunction in these diseases, recent studies on neurodegeneration and cognitive dysfunction have demonstrated a significant impact of receptor modulation on cognitive changes. The pathological alterations in various receptors appear to contribute to cognitive impairment and/or deterioration with correlation to diversified mechanisms. This article recapitulates the present understandings and concepts underlying the modulation of different receptors in human beings and various experimental models of Alzheimer's disease and Parkinson's disease as well as a conceptual update on the underlying mechanisms. Specific roles of serotonin, adrenaline, acetylcholine, dopamine receptors, and N-methyl-d-aspartate receptors in Alzheimer's disease and Parkinson's disease will be interactively discussed. Complex mechanisms involved in their signaling pathways in the cognitive dysfunction associated with the neurodegenerative diseases will also be addressed. Substantial evidence has suggested that those receptors are crucial neuroregulators contributing to cognitive pathology and complicated correlations exist between those receptors and the expression of cognitive capacities. The pathological alterations in the receptors would, therefore, contribute to cognitive impairments and/or deterioration in Alzheimer's disease and Parkinson's disease. Future research may shed light on new clues for the treatment of cognitive dysfunction in neurodegenerative diseases by targeting specific alterations in these receptors and their signal transduction pathways in the frontal–striatal, fronto–striato–thalamic, and mesolimbic circuitries.

► Cognitive dysfunction is a characteristic of neurodegenerative diseases, especially AD and PD.
► Pathophysiological alterations in monoamine, acetylcholine and glutamate receptors contribute to cognitive impairment and/or deterioration.
► Abnormalities of serotonin-, adrenaline-, dopamine-, acetylcholine- and NMDA-signaling pathways differentially contribute to the pathogenesis of such cognitive dysfunction.
► We may provide novel insights into better solutions of cognitive dysfunction by targeting specific mechanisms underlying the alterations in these receptors and their signal transduction in the frontal–striatal, fronto–striato–thalamic, and mesolimbic circuitries.