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Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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Role of ER in the Secretory Pathway01:17

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Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
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About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
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The Unfolded Protein Response01:37

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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Overview of Cell Death01:30

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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Necrosis01:16

Necrosis

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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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The Extrinsic Apoptotic Pathway01:17

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Related Experiment Video

Updated: Aug 18, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
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Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death.

Adalberto Merighi1, Laura Lossi1

  • 1Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.

International Journal of Molecular Sciences
|December 11, 2022
PubMed
Summary
This summary is machine-generated.

The endoplasmic reticulum (ER) manages protein folding and cellular homeostasis. This review explores how the unfolded protein response (UPR) in neurons balances cell survival and death under ER stress.

Keywords:
apoptosisautophagycerebellar granule cellsendoplasmic reticulumendoplasmic reticulum stressunfolded protein response

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Area of Science:

  • Cellular Biology
  • Neuroscience
  • Molecular Biology

Background:

  • The endoplasmic reticulum (ER) performs critical functions beyond protein processing, including lipid synthesis and calcium homeostasis.
  • Proper protein folding and modification within the ER depend on molecular chaperones and a stable environment.
  • Cellular stress disrupts ER conditions, activating signaling pathways like the unfolded protein response (UPR).

Purpose of the Study:

  • To review the intricate connections between UPR signaling, cell-protective mechanisms, and cell death.
  • To specifically focus on the mechanisms of ER stress and UPR in neuronal cells.
  • To elucidate how UPR activation influences neuronal survival or demise.

Main Methods:

  • Literature review of existing research on ER stress and UPR.
  • Analysis of signaling cascades involved in the unfolded protein response.
  • Examination of cell death pathways triggered by ER stress in neurons.

Main Results:

  • The UPR is a critical adaptive mechanism to restore ER homeostasis under stress.
  • Autophagy can be induced by UPR to preserve cellular integrity.
  • Dysfunctional or insufficient UPR signaling leads to cell death, particularly in neurons.

Conclusions:

  • The UPR plays a dual role in cell survival and death, contingent on its efficacy.
  • Understanding UPR mechanisms in neurons is crucial for addressing neurological disorders linked to ER stress.
  • Targeting UPR pathways may offer therapeutic strategies for neurodegenerative diseases.