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Updated: Aug 7, 2026

Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases
Published on: June 28, 2019
Proteasomal inhibition causes loss of nigral tyrosine hydroxylase neurons
Anthony H V Schapira1, Michael W J Cleeter, John R Muddle
1University Department of Clinical Neurosciences, Royal Free and University College, Medical School, London, United Kingdom. schapira@medsch.ucl.ac.uk
Abstract:
Dysfunction of the ubiquitin-proteasomal system (UPS) has been implicated in the pathogenesis of Parkinson's disease. The systemic administration of UPS inhibitors has been reported to induce nigrostriatal cell death and model Parkinson's disease pathology in rodents. We administered a synthetic, specific UPS inhibitor (PSI) subcutaneously to rats and quantified substantia nigral tyrosine hydroxylase-positive dopaminergic neurons by stereology. PSI caused a 15% decrease in UPS activity at 2 weeks and a 42% reduction in substantia nigra pars compacta tyrosine hydroxylase-positive neurons at 8 weeks. Systemic inhibition of the UPS warrants further evaluation as a means to model Parkinson's disease.
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