ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.
Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Diabetic Retinopathy and Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Epidemiological Associations and Clinical Implications.Journal of diabetes research · 2026Pooled it
- The lithium-magnesium-zinc axis under stress: regulation of N-glycosylation-linked proteostasis and Alzheimer's disease.Inflammopharmacology · 2026Article
- The IRE1-XBP1s Axis Drives Inflammatory Osteolysis by Regulating a 5-HT Dependent Endogenous Anti-Autophagy Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.Investigative ophthalmology & visual science · 2026Review
- Age-Related Neurovascular Dysfunction in the Retina and Potential Pathogenic Mechanisms.Investigative ophthalmology & visual science · 2026Review
- Mitochondrial ROS in Retinal Neurodegeneration: Thresholds, Quality Control Failure, and Precision Therapeutic Windows.Biomolecules · 2026Review
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Association between diabetic retinopathy and neurodegenerative diseases in the All of Us research program.AJO international · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Diabetic retinopathy (DR) and Alzheimer's disease (AD) are progressive neurodegenerative disorders affecting the eye and the brain, respectively. Despite targeting different organs, they share common molecular mechanisms. A central process connecting these conditions is the unfolded protein response (UPR), which maintains protein homeostasis in the endoplasmic reticulum (ER). Dysregulation of UPR pathways, particularly the IRE1-XBP1 and PERK-eIF2α pathways, can lead to inflammation, oxidative stress, and neurodegeneration. While the IRE1-XBP1 pathway regulates protein folding and inflammatory signaling, the PERK-eIF2α pathway reduces protein synthesis but may trigger apoptosis if persistently activated. Emerging therapies targeting UPR pathways and ER chaperones show promise in mitigating neurodegenerative damage in DR and AD. This review highlights shared pathophysiological mechanisms, explore retinal biomarkers for early AD detection, and emphasizes UPR modulation as a therapeutic strategy for neurodegeneration in aging-related diseases. HIGHLIGHTS: Diabetic retinopathy (DR, ocular disorder) and Alzheimer's disease (AD, cerebral disorder) share common molecular mechanisms, including oxidative stress, inflammation, and proteostasis dysfunction. UPR is a critical pathway linking both diseases through endoplasmic reticulum (ER) stress and neurodegeneration and targeting unfolded protein response (UPR) pathways, ER chaperones (e.g., P58IPK), and anti-inflammatory treatments show promise. The IRE1-XBP1 pathway regulates protein homeostasis and inflammation; XBP1s protects against ER stress in both retinal and brain neurons. The PERK-eIF2α pathway suppresses protein synthesis under stress but may induce apoptosis via ATF4 and CHOP if chronically activated. Age-related decline in metabolism, proteostasis, and neurovascular function intensifies disease progression and exacerbates molecular and cellular damage in both DR and AD.
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Registered trials
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 OpenQuestion graph.