Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/171258
Title: Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases
Author: Cai, Rong
Zhang, Yu
Simmering, Jacob E.
Schultz, Jordan L.
Li, Yuhong
Fernandez-Carasa, Irene
Consiglio, Antonella
Raya, Angel
Polgreen, Philip M.
Narayanan, Nandakumar S.
Yuan, Yanpeng
Chen, Zhiguo
Su, Wenting
Han, Yanping
Zhao, Chunyue
Gao, Lifang
Ji, Xunming
Welsh, Michael J.
Li, Lei
Keywords: Malaltia de Parkinson
Malalties neurodegeneratives
Parkinson's disease
Neurodegenerative Diseases
Issue Date: 1-Oct-2019
Publisher: American Society for Clinical Investigation
Abstract: Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.
Note: Reproducció del document publicat a: https://doi.org/10.1172/JCI129987
It is part of: Journal of Clinical Investigation, 2019, vol. 129, num. 10, p. 4539-4549
URI: http://hdl.handle.net/2445/171258
Related resource: https://doi.org/10.1172/JCI129987
ISSN: 0021-9738
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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