Murph
:)
- Messages
- 1,805
Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases.
Cai R1,2, Zhang Y3, Simmering JE4, Schultz JL5, Li Y2, Fernandez-Carasa I6, Consiglio A6,7, Raya A8,9, Polgreen PM10, Narayanan NS11, Yuan Y1, Chen Z1, Su W2, Han Y1, Zhao C12, Gao L2, Ji X1,2, Welsh MJ13, Liu L2,12.
Author information
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.
KEYWORDS:
Neuroscience; Parkinson’s disease
PMID: 31524631 DOI: 10.1172/JCI129987
Cai R1,2, Zhang Y3, Simmering JE4, Schultz JL5, Li Y2, Fernandez-Carasa I6, Consiglio A6,7, Raya A8,9, Polgreen PM10, Narayanan NS11, Yuan Y1, Chen Z1, Su W2, Han Y1, Zhao C12, Gao L2, Ji X1,2, Welsh MJ13, Liu L2,12.
Author information
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.
KEYWORDS:
Neuroscience; Parkinson’s disease
PMID: 31524631 DOI: 10.1172/JCI129987
