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Cited by 261Endoplasmic Reticulum Stress and DiseaseAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

ER stress and UPR in Alzheimer’s disease: mechanisms, pathogenesis, treatments

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Ajoolabady, Amir, Lindholm, Dan, Ren, Jun, Pratico, Domenico·2022·Cell Death & Disease
DOI 10.1038/s41419-022-05153-5PMC PMC9378716
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Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of Aβ to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the unique role of ER stress in AD pathogenesis, reviewing key findings, and existing controversy in an attempt to summarize plausible therapeutic interventions in the management of AD pathophysiology.

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  • AD pathology induces ER stress and excessive UPR activation.

    “Since AD pathology induces ER stress and excessive UPR activation [28]”

    From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [28]

    The Facts section says Aβ and tau deposition induce ER stress, but distinguishes adaptive UPR in response to mild stress from excessive, maladaptive UPR associated with advanced AD pathology. The claim omits that stage-dependent qualification and implies excessive activation follows AD pathology generally. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Ajoolabady, A., Lindholm, D., Ren, J., & Pratico, D.
Affiliations
  • Fudan University (CN)
  • University of Helsinki (FI)
  • University of Washington (US)
Corresponding author
Ren, Jun
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2022-08-15
Volume
13
Issue
8
Pages
706-706
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-022-05153-5
PMC
PMC9378716
OpenAlex
W4291464609
Cited by
261
References
12
Citations by year
2026: 72 · 2025: 87 · 2024: 68 · 2023: 32 · 2022: 2
FWCI
6.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • TUScholarShare (Temple University) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, endoplasmic reticulum stress, unfolded protein response, protein misfolding, neurodegeneration, therapeutic interventions, pathogenesis
MeSH terms
Alzheimer Disease, Humans, Unfolded Protein Response, Endoplasmic Reticulum Stress

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