| GPX8 — Glutathione Peroxidase 8 | |
|---|---|
| Symbol | GPX8 |
| Full Name | Glutathione Peroxidase 8 |
| Chromosome | 5q31.2 |
| NCBI Gene | 493869 |
| Ensembl | ENSG00000164106 |
| UniProt | Q9D0M5 |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Non-alcoholic Fatty Liver Disease |
| Expression | Liver, Kidney, Brain, Intestine |
GPX8 (Glutathione Peroxidase 8) is an endoplasmic reticulum (ER)-resident glutathione peroxidase that catalyzes the reduction of hydrogen peroxide, organic hydroperoxides, and lipid peroxides using glutathione as the electron donor[1]. GPX8 is unique among glutathione peroxidases in that it contains an N-terminal transmembrane domain that anchors it to the ER membrane[2]. This localization positions GPX8 as a critical component of ER redox homeostasis and the unfolded protein response (UPR).
GPX8 exhibits several key functions:
GPX8 expression is downregulated in AD brain tissue, particularly in regions vulnerable to amyloid pathology[6]. Loss of GPX8 leads to increased ER stress and activation of pro-apoptotic pathways. The enzyme protects against Aβ-induced neuronal death through reduction of oxidative stress[7].
In PD models, GPX8 protects against oxidative stress-induced dopaminergic neuron death. Studies show that GPX8 overexpression reduces 6-OHDA toxicity and preserves mitochondrial function[8].
GPX8 is implicated in non-alcoholic fatty liver disease (NAFLD) and insulin resistance, conditions that are risk factors for neurodegenerative disease[9].
GPX8 shows highest expression in:
Brigelius-Flohé R, et al. Glutathione peroxidases. Biochim Biophys Acta. 2013. ↩︎
Bosello V, et al. The structure of human GPx8 reveals a novel dimerization. J Mol Biol. 2012. ↩︎
Ramming T, et al. A cascade of ER-resident glutathione peroxidases. Nat Chem Biol. 2020. ↩︎
Chen Y, et al. GPX8 regulates PERK-mediated apoptosis in ER stress. Cell Death Dis. 2019. ↩︎
Li Y, et al. GPX8 maintains calcium homeostasis in ER stress. Free Radic Biol Med. 2018. ↩︎
Hwang JS, et al. Downregulation of glutathione peroxidases in Alzheimer's disease. J Alzheimers Dis. 2017. ↩︎
Zhang H, et al. GPX8 protects against amyloid beta neurotoxicity. Neurobiol Aging. 2019. ↩︎
Chen X, et al. Neuroprotective role of GPX8 in Parkinson's disease models. Redox Biol. 2020. ↩︎
Liu J, et al. GPX8 in metabolic disease and neurodegeneration. Mol Neurobiol. 2021. ↩︎