Evidence map›Paper›PMID 41275935›Full record

ArticleFree radical biology & medicine2026

APOE4 impairs Nrf2-PINK1/Parkin-dependent mitochondrial clearance through disrupted antioxidant and mitophagy signaling.

Firoz Akhter, Asma Akhter, Donghui Zhu

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PubMed Full text at PMC Publisher
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Article in Free radical biology & medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Firoz AkhterDepartment of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, United States.
Asma AkhterDepartment of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, United States.
Donghui ZhuDepartment of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, United States; Neuroscience Graduate Program, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794, United States. Electronic address: donghui.zhu@stonybrook.edu.

Funding

Novel surface-modified bioresorbable zinc-based stent materialsR01HL140562 · NHLBI · UNIVERSITY OF NORTH TEXAS · PI Ke Cheng, Donghui Zhu · 2018 to 2026
$4.3M
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's DiseaseR01AG064798 · NIA · STATE UNIVERSITY NEW YORK STONY BROOK · PI ZHU, DONGHUI · 2019 to 2023
$3.6M
Bioresorbable Zinc Staples for Anastomoses in the Digestive TractR01DK129493 · NIDDK · STATE UNIVERSITY NEW YORK STONY BROOK · PI Donghui Zhu · 2022 to 2026
$3.2M
NHLBI NIH HHS R01 HL140562NIA NIH HHS R01 AG064798NIDDK NIH HHS R01 DK129493
6 · The paper itself

Abstract

APOE4, the strongest genetic risk factor for sporadic Alzheimer's disease (AD), is closely associated with mitochondrial dysfunction, yet the mechanisms remain poorly defined. We identify a previously unrecognized failure of the Nrf2-PINK1/Parkin axis in APOE4 neurons that compromises mitochondrial quality control. Unlike APOE3, APOE4 neurons fail to activate PINK1/Parkin-dependent mitophagy under stress, a defect compounded by impaired Nrf2 signaling and weakened antioxidant defenses. In vivo, APOE4 mice show age-dependent collapse of this pathway, correlating with progressive mitochondrial dysfunction and disrupted mito-nuclear communication. Pharmacological activation of Nrf2 or PINK1 restores mitochondrial clearance, highlighting the axis as a druggable node. These findings provide a mechanistic link between APOE4 and mitochondrial failure, establishing the Nrf2-PINK1/Parkin pathway as a critical driver of neurodegeneration and a promising target for therapeutic intervention in AD.

Indexed as

Alzheimer DiseaseApolipoprotein E4MitochondriaMitophagyNF-E2-Related Factor 2Protein KinasesUbiquitin-Protein LigasesAnimalsAntioxidantsHumansMiceNeuronsOxidative StressPTEN-Induced Putative KinaseSignal TransductionAntioxidantsApolipoprotein E4Nfe2l2 protein, mouseNF-E2-Related Factor 2parkin proteinProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein LigasesAlzheimer's disease (AD)APOE4Mitochondrial stressMito-nuclear communicationMitophagyNrf2-PINK/Parkin

Identifiers

PMID41275935
PMCPMC13539568

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.