Thioredoxin reductase 2, mitochondrial

Thioredoxin reductase 2 (TXNRD2) is a mitochondrial enzyme that maintains thioredoxin in a reduced state and regulates mitochondrial redox homeostasis by controlling reactive oxygen species levels (UniProt: Q9NNW7). The protein plays a role in redox-regulated cell signaling. TXNRD2 mutations are associated with glucocorticoid deficiency type 5 (GCCD5), a rare autosomal recessive disorder affecting adrenal function.

In Alzheimer's disease, TXNRD2 is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change −0.13; Chaparral AD proteomics). The down-regulation was detected across subcellular fractions using TMT-labeled quantitative proteomics. This reduced expression may compromise mitochondrial antioxidant capacity, potentially contributing to the oxidative stress and mitochondrial dysfunction characteristic of AD pathology.