Stress-induced nuclear GAPDH: Scientific update and clinical application
Parimala Vedula1, Koko Ishizuka2, Arisa Hayashida2
1Departments of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Summary
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a moonlighting protein. Stress-induced nuclear GAPDH triggers cellular dysfunction, but blocking this pathway shows limited clinical success for neurological diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) exhibits moonlighting functions beyond glycolysis.
- Stress triggers GAPDH nuclear translocation, leading to cellular dysfunction and death.
Purpose of the Study:
- To review the scientific frontline of stress-induced nuclear GAPDH.
- To discuss its potential and limitations in clinical applications for neurological and psychiatric diseases.
Main Methods:
- Literature review of studies on GAPDH nuclear translocation.
- Analysis of preclinical and clinical trial data for compounds targeting the GAPDH cascade.
Main Results:
- Stress-induced nuclear GAPDH is a reproducible phenomenon linked to cellular damage.
- Small compounds show promise in preclinical models but faced clinical trial failures (e.g., Omigapil for Parkinson's disease, ALS).
Conclusions:
- Despite therapeutic potential, clinical translation of targeting nuclear GAPDH remains challenging.
- Further research is needed to overcome obstacles in developing effective treatments for related diseases.
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