title: Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models.
abstract: Meclizine is a well-tolerated drug routinely used as an anti-histamine agent in the management of disequilibrium. Recently, meclizine has been assessed for its neuroprotective properties in ischemic stroke and Huntington disease models. We found that meclizine protected against 6-hydroxydopamine-induced apoptosis and cell death in both SH-SY5Y cells and rat primary cortical cultures. Meclizine increases the level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which activates phosphofructokinase, a rate-determining enzyme of glycolysis. This protection is therefore mediated by meclizine's ability to enhance glycolysis and increase mitochondrial hyperpolarization. Meclizine represents an interesting candidate for further investigation to re-purpose for its potential to be neuroprotective in Parkinson disease.
authors.affiliation: Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, UK.|Department of Neurology, Shuang Ho Hospital, Taipei Medical University Taiwan.
authors.forename: Chien Tai
authors.initials: CT
authors.lastname: Hong
authors.affiliation: Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, UK.
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Chau
authors.affiliation: Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, UK.
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D005635:Fructosediphosphates / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008468:Meclizine / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000378:metabolism; D025221:Phosphofructokinases / Q000378:metabolism; D051381:Rats
chemical_list: D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D008468:Meclizine; C027652:fructose 2,6-diphosphate; D016627:Oxidopamine; D025221:Phosphofructokinases; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2