Exploring the Endoplasmic Reticulum's Role in Alzheimer's Disease and Its Potential as a Therapeutic Target
Raed Obaid Saleh1, Majid S Jabir2, Jaafaru Sani Mohammed3
1Department of Medical Laboratories Techniques, College of Health and Medical Techniques, University of Al Maarif, Al Anbar, Iraq.
Journal of Biochemical and Molecular Toxicology
|July 28, 2025
Summary
Alzheimer's disease involves endoplasmic reticulum (ER) stress, disrupting protein folding and leading to neuronal death. Targeting ER stress pathways offers potential new treatments for this neurodegenerative condition.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia.
- The precise mechanisms driving AD pathogenesis remain incompletely understood.
- Endoplasmic reticulum (ER) dysfunction, leading to ER stress, is increasingly implicated in AD development.
Purpose of the Study:
- To review the critical role of the endoplasmic reticulum (ER) in Alzheimer's disease (AD).
- To elucidate the mechanisms by which ER dysfunction exacerbates AD progression.
- To evaluate emerging therapeutic strategies targeting ER stress for AD treatment.
Main Methods:
- Literature review of studies investigating ER function in AD.
- Analysis of research on ER stress, unfolded protein response (UPR), and AD hallmarks (amyloid-beta plaques, tau hyperphosphorylation).
- Evaluation of preclinical and clinical data on ER-targeted therapies for AD.
Main Results:
- ER stress is a significant contributor to AD pathogenesis, linked to protein misfolding and neuronal dysfunction.
- The unfolded protein response (UPR) can promote neuronal cell death when chronically activated by ER stress in AD.
- ER stress pathways interact with amyloid-beta accumulation and tau hyperphosphorylation, key features of AD.
- Targeting ER stress shows promise in preclinical models for mitigating AD pathology and symptoms.
Conclusions:
- Endoplasmic reticulum stress is a central mechanism in Alzheimer's disease progression.
- Restoring ER homeostasis presents a viable therapeutic strategy for Alzheimer's disease.
- Further research into ER-targeted interventions is warranted to develop effective treatments for AD.
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