Glutathione S-transferase hGSTM3 and ageing-associated neurodegeneration: relationship to Alzheimer's disease

Glutathione S-transferases (GSTs) are detoxification enzymes that can counter ageing-associated oxidative and chemical stresses. The transcript of a distinct subclass of human GSTs (hGSTM3) was shown by RNA blot analysis to be widely distributed in different regions of adult brain. HPLC profiles indicated that the hGSTM3 subunit was the second most abundant GST subunit in brain. Immunocytochemistry performed with hGSTM3-specific antisera, showed prominent staining of neuritic plaques, neurofibrillary tangles and microglia in sections of hippocampus obtained from patients with Alzheimer's disease. The staining pattern was distinct from that obtained with normal brains. Because hGSTM3 is rich in cysteine residues and readily undergoes S-glutathiolation reactions, deposition of this protein could originate from cross-links produced by oxidative stress.