Possible involvement of endoplasmic reticulum stress in the pathogenesis of Alzheimer’s disease

Abstract

The endoplasmic reticulum (ER) is an organelle that plays a crucial role in protein quality control such as protein folding. Evidence to indicate the involvement of ER in maintaining cellular homeostasis is increasing. However, when cells are exposed to stressful conditions, which perturb ER function, unfolded proteins accumulate leading to ER stress. Cells then activate the unfolded protein response (UPR) to cope with this stressful condition. In the present review, we will discuss and summarize recent advances in research on the basic mechanisms of the UPR. We also discuss the possible involvement of ER stress in the pathogenesis of Alzheimer’s disease (AD). Potential therapeutic opportunities for diseases targeting ER stress is also described.

Link between endoplasmic reticulum stress and autophagy in neurodegenerative diseases

“…Triggered by the ER stress, the unfolded protein response (UPR) is activated in the cell. There is increasing evidence for the involvement of ER stress in various diseases such as neurodegenerative diseases, diabetes, obesity, and cancer (2)(3)(4)(5). In the context of neurodegenerative diseases, the present review describes the recent findings of the mechanisms of UPR, ER stress as a causative for neurodegenerative diseases, ER stress-induced apoptosis and autophagy involved in ER stress.…”

Complexity across scales: a walkthrough to linking neuro-imaging readouts to molecular processes

“…This could trigger ADAM10 to partially compete with the gamma-secretase for APP fragment resulting in the activation of Notch signaling pathway which is well-known for neuronal repair [159][160][161]. However, in case of AD ADAM mutant Q170H and R181G does not compete with alpha-secretase, therefore the beta-secretases accumulate in the brain resulting in impaired cerebral blood flow [162][163][164].…”

Neuroprotective Effects of 4-phenylbutyric Acid and Its Derivatives: Possible Therapeutics for Neurodegenerative Diseases

“…The aggregation of nascent or denatured proteins is considered to be a major factor in the pathogenesis of neurodegenerative diseases, as this aggregation can induce endoplasmic reticulum (ER) stress. For further details, the reader is directed to Hosoi et al (2015), who thoroughly reviewed the relationship between Alzheimer's disease (AD) and endoplasmic reticulum stress [9].…”