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The bloodbrain barrier tightly regulates brain extracellular composition of glutamine, glutamate and GABA irrespective of the level in the blood (Reference Hawkins and Vina46,Reference Dolgodilina, Imobersteg and Laczko47)

While the UPR initially enhances proteasome activity to manage misfolded proteins, chronic ER stress can overwhelm the UPS, compromise proteasome function and exacerbate cellular dysfunction