Glutathione S-transferase A4 (GSTA4)

Glutathione S-transferase A4 (GSTA4) is a cytosolic enzyme belonging to the alpha class of the glutathione S-transferase superfamily, which plays a critical role in cellular detoxification by conjugating reduced glutathione to electrophilic compounds (UniProt [1], GeneCards [4]). It is uniquely characterized by its high catalytic efficiency toward 4-hydroxynonenal (4-HNE), a major toxic byproduct of lipid peroxidation that can cause DNA damage and protein modification (Wikipedia [6], MDPI [8]). In healthy tissues, GSTA4 serves a protective function against oxidative stress, and its downregulation in adipose tissue is linked to mitochondrial dysfunction, insulin resistance, and obesity (PMC [19]). Conversely, in various malignancies such as colorectal and hepatocellular carcinoma, GSTA4 is often overexpressed, where it promotes tumor cell proliferation, metastasis, and resistance to chemotherapeutic agents like 5-fluorouracil and oxaliplatin (PMC [11], PubMed [16]). Because of this dual role, GSTA4 is considered a promising therapeutic target; inhibitors are being investigated to sensitize resistant tumors to treatment, while activators or inducers are explored for their potential to mitigate oxidative damage in neurodegenerative and metabolic diseases (PMC [12], MDPI [15]).

Other names

Glutathione S-transferase A4-4GSTA4-4GST class-alpha member 4GTA4S-(Hydroxyalkyl)glutathione lyase A4Glutathione S-aralkyltransferase A4Glutathione S-alkyltransferase A4Glutathione S-aryltransferase A4GST 8-8GST 5.7

GSTA4-4 is targeted either through direct inhibition to increase intracellular levels of toxic 4-hydroxynonenal (4-HNE) and reactive oxygen species (ROS), thereby sensitizing cancer cells to apoptosis and chemotherapy, or through induction/activation to enhance the detoxification of lipid peroxidation products and protect against oxidative stress-induced damage in metabolic and neurodegenerative conditions.