Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC H4H 1R3, Canada.
Sorbonne Université, INSERM, CNRS, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France; Laboratoire des Biomolécules, LBM, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France.
Trends Pharmacol Sci. 2021 Jun;42(6):475-490. doi: 10.1016/j.tips.2021.03.003. Epub 2021 Mar 25.
Vesicular glutamate transporters (VGLUTs) were long thought to be specific markers of glutamatergic excitatory transmission. The discovery, two decades ago, of the atypical VGLUT3 has thoroughly modified this oversimplified view. VGLUT3 is strategically expressed in discrete populations of glutamatergic, cholinergic, serotonergic, and even GABAergic neurons. Recent reports show the subtle, but critical, implications of VGLUT3-dependent glutamate co-transmission and its roles in the regulation of diverse brain functions and dysfunctions. Progress in the neuropharmacology of VGLUT3 could lead to decisive breakthroughs in the treatment of Parkinson's disease (PD), addiction, eating disorders, anxiety, presbycusis, or pain. This review summarizes recent findings on VGLUT3 and its vesicular underpinnings as well as on possible ways to target this atypical transporter for future therapeutic strategies.
囊泡谷氨酸转运体（VGLUTs）长期以来被认为是谷氨酸能兴奋性传递的特异性标志物。二十年前，非典型 VGLUT3 的发现彻底改变了这种过于简单的观点。VGLUT3 选择性地表达在离散的谷氨酸能、胆碱能、血清素能甚至 GABA 能神经元群体中。最近的报告显示，VGLUT3 依赖的谷氨酸共传递及其在调节多种脑功能和功能障碍中的作用具有微妙但关键的意义。VGLUT3 的神经药理学进展可能会在帕金森病（PD）、成瘾、饮食失调、焦虑、老年性聋或疼痛的治疗方面取得决定性突破。本综述总结了最近关于 VGLUT3 及其囊泡基础以及针对这种非典型转运体的未来治疗策略的可能靶向方法的发现。
