The Unfolded Protein Response: A Double-Edged Sword for Brain Health.
Magdalena GebertJakub SławskiBogusław NedoszytkoJames F CollawnRafał BartoszewskiPublished in: Antioxidants (Basel, Switzerland) (2023)
Efficient brain function requires as much as 20% of the total oxygen intake to support normal neuronal cell function. This level of oxygen usage, however, leads to the generation of free radicals, and thus can lead to oxidative stress and potentially to age-related cognitive decay and even neurodegenerative diseases. The regulation of this system requires a complex monitoring network to maintain proper oxygen homeostasis. Furthermore, the high content of mitochondria in the brain has elevated glucose demands, and thus requires a normal redox balance. Maintaining this is mediated by adaptive stress response pathways that permit cells to survive oxidative stress and to minimize cellular damage. These stress pathways rely on the proper function of the endoplasmic reticulum (ER) and the activation of the unfolded protein response (UPR), a cellular pathway responsible for normal ER function and cell survival. Interestingly, the UPR has two opposing signaling pathways, one that promotes cell survival and one that induces apoptosis. In this narrative review, we discuss the opposing roles of the UPR signaling pathways and how a better understanding of these stress pathways could potentially allow for the development of effective strategies to prevent age-related cognitive decay as well as treat neurodegenerative diseases.
Keyphrases
- endoplasmic reticulum
- oxidative stress
- induced apoptosis
- signaling pathway
- resting state
- white matter
- cerebral ischemia
- endoplasmic reticulum stress
- healthcare
- dna damage
- public health
- functional connectivity
- ischemia reperfusion injury
- mental health
- diabetic rats
- amino acid
- protein protein
- binding protein
- type diabetes
- cell death
- stress induced
- body mass index
- epithelial mesenchymal transition
- risk assessment
- pi k akt
- subarachnoid hemorrhage
- physical activity
- cell proliferation
- multiple sclerosis
- estrogen receptor
- insulin resistance
- metabolic syndrome
- weight loss
- heat stress
- health information
- blood brain barrier