Pavan Barbara, Dalpiaz Alessandro
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
Neural Regen Res. 2017 Sep;12(9):1401-1404. doi: 10.4103/1673-5374.215246.
The expression of ectopic olfactory receptors (ORs) in melanized cells, such as the human brain nigrostriatal 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 α-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pigmentation 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 neurodegenerative dysfunctions, including melanoma and Parkinson's disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VN1R1 is proposed, helping to counteract female susceptibility to Parkinson's disease in quiescent life.
本文指出了异位嗅觉受体（ORs）在黑色素化细胞中的表达，如人类大脑黑质纹状体多巴胺能神经元和皮肤黑素细胞。已知ORs可调节皮肤黑色素生成，而在以色素神经黑色素积累为特征的多巴胺能神经元中，OR表达在帕金森病中下调。此外，还强调了色素沉着过程与通过α-突触核蛋白表达的多巴胺途径之间的相关性。特意地，这些ORs被建议作为与色素沉着障碍相关的神经退行性疾病的治疗靶点。基于这一证据，因此引入了一种将气味剂转化为药物的可能方法，作用于三种特定的嗅觉受体，即OR51E2、OR2AT4和VN1R1。各种气味分子被证明与这些ORs相互作用，并提示了它们对黑色素生成和神经退行性功能障碍（包括黑色素瘤和帕金森病）的治疗潜力。最后，提出了人类大脑中嗅觉和内分泌系统通过VN1R1的直接功能联系，有助于抵消女性在平静生活中对帕金森病的易感性。
