Phosphoglycerate kinase 1 as a therapeutic target in neurological disease

Harriet McHale-Owen; Kiterie M.E. Faller; Helena Chaytow; Thomas H. Gillingwater

doi:10.1016/j.molmed.2025.03.008

Phosphoglycerate kinase 1 as a therapeutic target in neurological disease

Harriet McHale-Owen, Kiterie M.E. Faller, Helena Chaytow, Thomas H. Gillingwater^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson’s disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.

Original language	English
Number of pages	12
Journal	Trends in Molecular Medicine
Early online date	14 Apr 2025
DOIs	https://doi.org/10.1016/j.molmed.2025.03.008
Publication status	E-pub ahead of print - 14 Apr 2025

Keywords / Materials (for Non-textual outputs)

neurodegeneration
amyotrophic lateral sclerosis
spinal muscular atrophy
terazosin
therapy development

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10.1016/j.molmed.2025.03.008Licence: Creative Commons: Attribution (CC-BY)

Phosphoglycerate kinase 1 as a therapeutic target in neurological diseaseFinal published version, 1.05 MBLicence: Creative Commons: Attribution (CC-BY)

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title = "Phosphoglycerate kinase 1 as a therapeutic target in neurological disease",

abstract = "Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson{\textquoteright}s disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.",

keywords = "neurodegeneration, amyotrophic lateral sclerosis, spinal muscular atrophy, terazosin, therapy development",

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AU - McHale-Owen, Harriet

AU - Faller, Kiterie M.E.

AU - Chaytow, Helena

AU - Gillingwater, Thomas H.

PY - 2025/4/14

Y1 - 2025/4/14

N2 - Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson’s disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.

AB - Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson’s disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.

KW - neurodegeneration

KW - amyotrophic lateral sclerosis

KW - spinal muscular atrophy

KW - terazosin

KW - therapy development

U2 - 10.1016/j.molmed.2025.03.008

DO - 10.1016/j.molmed.2025.03.008

M3 - Article

SN - 1471-4914

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

ER -

Phosphoglycerate kinase 1 as a therapeutic target in neurological disease

Abstract

Keywords / Materials (for Non-textual outputs)

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