Phosphoglycerate kinase 1 as a therapeutic target in neurological disease

The glycolytic enzyme phosphoglycerate kinase 1 (PGK1) has emerged as a promising therapeutic target for both Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). 

Enhancing glycolysis represents an attractive approach because neurons are particularly vulnerable to dysregulated cell metabolism.

Although clinical trials of the PGK1 agonist terazosin are underway for PD and ALS, this compound can generate significant side effects, highlighting the need to identify alternative PGK1-activating strategies and compounds.

The potential benefits of increasing PGK1 activity in other neurological conditions are less clear.

Further understanding of the noncanonical roles of PGK1 is needed to determine in which conditions increased activation may be beneficial.

https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(25)00059-0

https://sciencemission.com/PGK1--therapeutic-target-in-neurological-disease