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Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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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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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
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
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Recycling Endosomes and Transcytosis00:58

Recycling Endosomes and Transcytosis

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The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
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The Early Endosome: Endocytosis of Transferrin01:28

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Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
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Export of Misfolded Proteins out of the ER01:32

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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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The Proteasome01:13

The Proteasome

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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Related Experiment Video

Updated: Jul 13, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
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Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

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The endolysosomal pathway and ALS/FTD.

Tiffany W Todd1, Wei Shao1, Yong-Jie Zhang2

  • 1Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Trends in Neurosciences
|October 12, 2023
PubMed
Summary
This summary is machine-generated.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are linked to the endolysosomal system. Disrupting this system, not just autophagy, may be key to ALS and FTD progression.

Keywords:
C9ORF72TDP-43TMEM106Bautophagyneurodegenerationproteinopathy

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Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlapping genetic links.
  • Several genes implicated in ALS/FTD are connected to the endolysosomal pathway.
  • The role of endolysosomal dysfunction in ALS/FTD pathogenesis is increasingly recognized.

Purpose of the Study:

  • To review the intricate connections between ALS/FTD and the endolysosomal system.
  • To elucidate how disease-associated genes impact the endolysosomal pathway.
  • To explore downstream consequences of endolysosomal disruption beyond autophagy.

Main Methods:

  • Literature review and synthesis of current research findings.
  • Analysis of genetic associations with the endolysosomal system in ALS/FTD.
  • Discussion of pathogenic mechanisms involving endolysosomal dysfunction.

Main Results:

  • Evidence suggests a strong link between ALS/FTD and the endolysosomal system.
  • Specific genes associated with ALS/FTD directly affect endolysosomal function.
  • Endolysosomal system disruption, rather than solely autophagy impairment, may drive disease pathology.

Conclusions:

  • The endolysosomal system is a critical player in the pathogenesis of ALS and FTD.
  • Targeting endolysosomal dysfunction presents a potential therapeutic avenue for ALS/FTD.
  • Further research into non-autophagy consequences of endolysosomal disruption is warranted.