Bursting the unfolded protein response accelerates axonal regeneration

Bursting the unfolded protein response accelerates axonal regeneration

Axonal Activation of the Unfolded Protein Response Promotes Axonal Regeneration Following Peripheral Nerve Injury

Adult mammalian peripheral neurons have an intrinsic regrowth capacity in response to axonal injury. The induction of calcium ion (Ca2+) oscillations at an injured site is critical for the regulation of regenerative responses. In polarized neurons, distal axonal segments contain a well-developed endoplasmic reticulum (ER) network that is responsible for Ca2+ homeostasis. Although these characte...

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found...

The unfolded protein response

Where does the UPR function? Between the endoplasmic reticulum (ER) and the nucleus of eukaryotic cells. All secreted proteins and proteins that reside in secretory compartments translocate as nascent peptide chains into the ER, where they may undergo folding, modification and assembly before assuming their functional conformations. The ER maintains a specialized oxidizing environment to aid ch...

The unfolded protein response.

The endoplasmic reticulum (ER) is a principal site for folding and maturation of transmembrane, secretory and ERresident proteins. Perturbations that alter ER homeostasis can lead to accumulation of unfolded proteins (UPs), which is a threat to all living cells. To cope with the stress, cells activate an intracellular signaling pathway – the unfolded protein response (UPR). The UPR is an integr...