Glutathione S-transferase P

Glutathione S-transferase P (GSTP1) is a 210-amino-acid enzyme that catalyzes the conjugation of reduced glutathione to hydrophobic electrophiles, playing a key role in cellular detoxification (UniProt: P09211). The protein also participates in prostaglandin metabolism and acts as a negative regulator of ferroptosis by protecting cells from reactive aldehydes such as 4-hydroxynonenal. Additionally, GSTP1 negatively regulates CDK5 activity, which is implicated in neurodegeneration.

GSTP1 is widely expressed and functions in Phase II xenobiotic metabolism and cytoprotection across multiple tissues. Its role in mitigating oxidative stress and ferroptotic cell death is particularly relevant to neuronal biology and neurodegeneration pathways.

In Alzheimer's Disease, GSTP1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of +0.51 across subcellular fractions. This upregulation may reflect an adaptive cellular response to elevated oxidative stress and ferroptotic pressure characteristic of AD pathology, suggesting GSTP1 induction as a compensatory neuroprotective mechanism in the disease.