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SCIENTIFIC LITERATURE · MED

Stress-induced nuclear GAPDH: Scientific update and clinical application.

Neurotherapeutics · 2025-09-03

DOI: 10.1016/j.neurot.2025.e00725PMID: 40903341

Open accessreview-article; Review; Journal ArticleOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known as a moonlighting protein beyond its original glycolytic function. Stress-induced nuclear translocation of GAPDH has been reproducibly reported, which results in variety types of cellular responses, including cell death and dysfunction. Blocking this stress-induced cascade has been regarded as a target of drug discovery and development for human disease conditions, particularly for neurological and psychiatric diseases. There are promising small compounds that can block this cascade in cell and animal models. Nevertheless, the clinical trials for Parkinson's disease and amyotrophic lateral sclerosis with one of these compounds Omigapil were unsuccessful. Including these failure cases, this review article discussed the scientific frontline of GAPDH, particularly stress-induced nuclear GAPDH, and its potential for clinical applications.

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