VGLUT2 in Parkinson’s disease: an emerging therapeutic target
Year: 2026
Type: article
Abstract: INTRODUCTION: Parkinson's disease is among the most common age-related neurodegenerative disorders today and characterized by midbrain dopamine neuron degeneration. However, this cell loss is not uniform. Though most dopamine neuron loss occurs in the substantia nigra, some ventral tegmental area and dorsal-tier substantia nigra dopamine neurons are relatively resistant to degeneration in Parkinson's disease. Yet, the mechanisms underlying this dopamine neuron resilience remain unclear. Novel insights into neuronal resilience are provided by evidence of a midbrain dopamine neuron subpopulation that expresses the vesicular glutamate transporter 2, VGLUT2, and is more resistant to cell loss in both preclinical models and clinically in Parkinson's disease. Thus, VGLUT2 expression has emerged as a defining signature difference between vulnerable versus resilient dopamine neuron subpopulations. AREAS COVERED: Here, we review recent developments in the potential mechanisms of dopamine neuron resilience and the therapeutic potential associated with boosting cellular resilience via VGLUT2. EXPERT OPINION: We discuss approaches to maximize VGLUT2-mediated dopamine neuron resiliency. This includes increasing the efficiency of vesicular sequestration of dopamine to decrease generation of cytotoxic reactive oxygen species and increasing levels of neuroprotective antioxidant glutathione. Taken together, VGLUT2-mediated pathways represent original directions to treat Parkinson's disease symptoms and modify disease progression.
Institution: University of Pittsburgh
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G136881053, G9000106595
OpenAlex ID: W7124730043