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Decoding Parkinson's Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations
Liu T, Kong X, Qiao J, Wei J.. Redox biology, 2025-07-23
Topic: Brain proteins, microglia and lab models
Parkinson's disease (PD), a complex neurodegenerative disorder characterized by selective loss of substantia nigra (SN) dopaminergic neurons, pathological aggregation of α-synuclein (α-syn), and chronic neuroinflammation, is fundamentally driven by redox imbalance and oxidative stress. Recent studies reveal that a dynamic interplay of programmed and non-programmed cell death mechanisms-amplified by oxidative damage-drives PD progression. Programmed cell death pathways include apoptosis (caspase-dependent mitochondrial/extrinsic pathways), necroptosis (eceptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) axis), pyroptosis (NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome/Gasdermin D (GSDMD)-mediated pore formation), PARthanatos (DNA damage-poly ADP-ribose polymerase (PARP-1)/apoptosis-inducing
Key findings
- Recent studies reveal that a dynamic interplay of programmed and non-programmed cell death mechanisms-amplified by oxidative damage-drives PD progression.
- Programmed cell death pathways include apoptosis (caspase-dependent mitochondrial/extrinsic pathways), necroptosis (eceptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) axis), pyroptosis (NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome/Gasdermin D (GSDMD)-mediated pore formation), PARthanatos (DNA damage-poly ADP-ribose polymerase (PARP-1)/apoptosis-inducing factor (AIF) cascade), ferroptosis (redox imbalance-driven lipid peroxidation/glutathione peroxidase 4 (GPX4) inactivation), disulfidptosis (disulfide stress from cystine metabolic collapse), and cuproptosis (mitochondrial lipoylated protein toxicity via copper-mediated oxidative damage), while non-programmed necrosis is triggered by energy collapse and calcium overload.
- Mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and oxidative stress act as central redox hubs, integrating multiple death pathways through reactive oxygen species (ROS) bursts (O 2 · - , H 2 O 2 , ·OH), calcium dysregulation, and metabolic abnormalities, forming a self-amplifying vicious cycle.
- Non-neuronal cells (e.g., microglia and astrocytes) exacerbate neuronal redox damage by releasing pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)), dysregulating iron/copper metabolism (enhancing Fenton chemistry), and suppressing autophagic flux.
Why it matters
This review discusses cell death pathways, oxidative stress and therapeutic innovations in Parkinson's disease. It is about Parkinson's disease, not Alzheimer's disease, so it has no implications for treating, curing or preventing Alzheimer's.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 46 of the 96 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Redox biology) |
| Journal's citation record | 2 / 4 | Redox Biology: journal h-index 209 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 99 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 55.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 3 / 4 | Cited 99 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 0 / 3 | Zhengzhou University: institution h-index 522 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40712453) |
| Free to read | 2 / 2 | Free to read |
| Points | 46 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 46 of the 96 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Liu, T., Kong, X., Qiao, J., & Wei, J. (2025). Decoding Parkinson's Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations. Redox biology. https://doi.org/10.1016/j.redox.2025.103787
Vancouver
Liu T, Kong X, Qiao J, Wei J. Decoding Parkinson's Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations. Redox biology. 2025. doi:10.1016/j.redox.2025.103787. PMID: 40712453.
BibTeX
@article{liu2025-40712453,
author = {Liu, T. and Kong, X. and Qiao, J. and Wei, J.},
title = {{Decoding Parkinson's Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations}},
journal = {Redox biology},
year = {2025},
doi = {10.1016/j.redox.2025.103787},
pmid = {40712453},
url = {https://doi.org/10.1016/j.redox.2025.103787}
}
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