Leveraging VGLUT3 Functions to Untangle Brain Dysfunctions

Mathieu Favier (1) , Nicolas Pietrancosta (2, 3) , Salah El Mestikawy (1) , Giuseppe Gangarossa (4)

1 Douglas Mental Health University Institute [Montréal]
2 IBPS - Institut de Biologie Paris Seine
3 LBM UMR 7203 - Laboratoire des biomolécules
4 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative

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.

Mots clés: VESICULAR GLUTAMATE TRANSPORTER; STRIATAL CHOLINERGIC INTERNEURONS; DOPA-INDUCED DYSKINESIA; QUINOLINE-2; 4-DICARBOXYLIC ACIDS; SYNAPTIC-TRANSMISSION; MOLECULAR-CLONING; NEURONS; INHIBITORS; IDENTIFICATION; CORELEASE

Domaines: Sciences du Vivant [q-bio]

Mathieu Favier, Nicolas Pietrancosta, Salah El Mestikawy, Giuseppe Gangarossa. Leveraging VGLUT3 Functions to Untangle Brain Dysfunctions. Trends in Pharmacological Sciences, 2021, 42 (6), pp.475-490. ⟨10.1016/j.tips.2021.03.003⟩. ⟨hal-03677218⟩