The expression of ectopic olfactory receptors （ORs） in melanized cells, such as the human brain nigrostri- atal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin mel...The expression of ectopic olfactory receptors （ORs） in melanized cells, such as the human brain nigrostri- atal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson＇s disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through ct-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pig- mentation disorders. Based on this evidence, a possible way of turning odorants into drugs, acting on three specific olfactory receptors, OR51E2, OR2AT4 and VN1R1, is thus introduced. Various odorous molecules are shown to interact with these ORs and their therapeutic potential against melanogenic and neurodegen- erative dysfunctions, including melanoma and Parkinson＇s disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VNIR1 is proposed, helping to counteract female susceptibility to Parkinson＇s disease in quiescent life.展开更多
基金supported by the University of Ferrara(F72I15000470005)in the frame of the project FAR2014
文摘The expression of ectopic olfactory receptors （ORs） in melanized cells, such as the human brain nigrostri- atal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson＇s disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through ct-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pig- mentation disorders. Based on this evidence, a possible way of turning odorants into drugs, acting on three specific olfactory receptors, OR51E2, OR2AT4 and VN1R1, is thus introduced. Various odorous molecules are shown to interact with these ORs and their therapeutic potential against melanogenic and neurodegen- erative dysfunctions, including melanoma and Parkinson＇s disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VNIR1 is proposed, helping to counteract female susceptibility to Parkinson＇s disease in quiescent life.
