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Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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Neural Regulation01:37

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Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
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Delivery Pathways to the Lysosome01:36

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
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Lysosomal Hydrolases01:22

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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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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Autophagy01:27

Autophagy

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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
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Related Experiment Video

Updated: Jul 26, 2025

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
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ER-phagy in neurodegeneration.

Melissa A Hill1, Alex M Sykes1, George D Mellick1

  • 1Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.

Journal of Neuroscience Research
|June 19, 2023
PubMed
Summary

Cellular aging and waste accumulation drive neurodegenerative diseases. Endoplasmic reticulum-phagy (ER-phagy) emerges as a key mechanism for maintaining neuronal health and combating these conditions.

Keywords:
ER-phagyautophagyendoplasmic reticulumneurodegeneration

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Area of Science:

  • Neurobiology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Neurodegenerative diseases like Alzheimer's and Parkinson's are linked to cellular aging and the buildup of cellular waste.
  • Autophagy, a cellular recycling process, is crucial for neuronal homeostasis, especially given neurons' vulnerability to protein aggregates and damaged organelles.
  • Disruptions in autophagy are implicated as a major pathogenic mechanism in these disorders.

Purpose of the Study:

  • To review current research on endoplasmic reticulum-phagy (ER-phagy).
  • To explore the role of ER-phagy in the context of neurodegenerative diseases.
  • To highlight ER-phagy as a novel cellular mechanism in neuronal health and disease.

Main Methods:

  • Literature review of existing research on ER-phagy.
  • Analysis of studies linking autophagy and neurodegeneration.
  • Examination of the role of ER-phagy in cellular stress responses.

Main Results:

  • Autophagy is critical for clearing cellular debris, including misfolded proteins and damaged organelles, which is vital for neuronal survival.
  • Endoplasmic reticulum-phagy (ER-phagy) is a newly identified pathway that regulates endoplasmic reticulum structure and stress responses.
  • Emerging evidence suggests ER-phagy plays a significant role in cellular mechanisms underlying neurodegenerative diseases.

Conclusions:

  • ER-phagy is a critical cellular process for maintaining neuronal homeostasis.
  • Dysregulation of ER-phagy may contribute to the pathogenesis of neurodegenerative disorders.
  • Targeting ER-phagy presents a potential therapeutic avenue for neurodegenerative diseases.