Fig. 10: Schematic representation of the role of impaired proteins synthesis in the loss of homeostatic functions by AD astrocytes. | Cell Death & Disease

Fig. 10: Schematic representation of the role of impaired proteins synthesis in the loss of homeostatic functions by AD astrocytes.

From: Protein synthesis inhibition and loss of homeostatic functions in astrocytes from an Alzheimer’s disease mouse model: a role for ER-mitochondria interaction

Fig. 10

Phosphorylation of eIF2α and reduction of protein synthesis in AD astrocytes occurs without induction of overt ER stress/UPR and activation of PERK (∼ER stress, ∼PERK and intermittent red line). A role of PKR, HRI and GCN2 kinases is to be determined (blue arrow and question mark). Alteration of ER-mitochondrial interaction could be a plausible candidate (10 nm, red arrowheads and red thick arrow), as well as a reduced ATP supply by mitochondria (curved red arrow). A role of protein misfolding and ER Ca2+ dyshomeostasis is hypothesized (? Misfolding, ? ER Ca2+). The deregulation of proteins synthesis may potentially result in impaired secretion (red intermittent arrows) of neurotrophic and neuroprotective molecules as well as impaired formation of extracellular matrix (SPARC, heat shock proteins (HSPs), Adhesion, ECM). Protein synthesis, p-eIF2α levels and homeostatic functions can be rescued by the chemical chaperone 4-PBA (green arrows).

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