| Property |
Value |
| Protein Name |
Glutathione S-transferase Pi 1 |
| Gene |
GSTP1 |
| UniProt ID |
P09211 |
| PDB ID |
17GS, 3GUS, 5ZMW |
| Molecular Weight |
~23 kDa |
| Subcellular Localization |
Cytoplasm, nucleus |
| Protein Family |
Pi class glutathione S-transferase family |
Glutathione S-transferase Pi 1 is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
The GSTP1 protein is a 198-amino acid detoxifying enzyme with distinct features:
- N-terminal thioredoxin-like fold: Contains GSH binding site
- C-terminal alpha-helical domain: Substrate binding pocket
- Catalytic triad: Tyr7, Asp98, Cys47 for catalysis
- Dimerization interface: Forms homodimers
- JNK binding motif: Interacts with c-Jun N-terminal kinase
GSTP1 is the most abundant GST in brain and exists in multiple isoforms.
GSTP1 is a critical detoxifying enzyme in the nervous system:
- Xenobiotic detoxification: Neutralizes electrophilic toxins
- Oxidative stress defense: Conjugates lipid peroxidation products
- Signal transduction: Modulates MAPK and JNK signaling
- Protein S-glutathionylation: Regulates protein function via GSH addition
- Anti-apoptotic function: Blocks caspase activation
- Inflammation regulation: Modulates NF-κB and inflammatory responses
- Drug resistance: Affects chemotherapy response in brain tumors
GSTP1 is implicated in AD pathogenesis:
- Oxidative stress: GSTP1 activity reduced in AD brain
- Amyloid interaction: Binds to Aβ, may modulate toxicity
- Protein aggregation: S-glutathionylation affects tau pathology
- Neuronal vulnerability: GSTP1 loss exacerbates neurodegeneration
GSTP1 involvement in PD:
- Dopamine metabolism: Handles toxic dopamine quinones
- MPTP susceptibility: Modifies vulnerability to MPTP
- Alpha-synuclein: Modulates α-syn aggregation
- Environmental toxins: Protects against pesticide toxicity
¶ ALS and Brain Tumors
- ALS: GSTP1 alterations in motor neuron disease
- Glioblastoma: High GSTP1 confers chemotherapy resistance
- Ethacrynic acid: GSTP1 inhibitor in cancer trials
- TLK117: GSTP1-directed prodrug therapy (preclinical)
- Glutathione analogs: Selective GSTP1 modulators
- S-glutathionylation inhibitors: Protect against pathological S-glutathionylation
- Gene therapy: Deliver GSTP1 to neurons
- Townsend & Tew, GSTP1 in disease (2003)
- Menon & boards, GSTP1 and neurodegeneration (2018)
- Singh, GSTP1 in PD models (2019)