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Related Concept Videos

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.
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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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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
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Related Experiment Video

Updated: Mar 15, 2026

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p62 improves AD-like pathology by increasing autophagy.

A Caccamo1, E Ferreira1, C Branca1

  • 1The Arizona State University-Banner Neurodegenerative Disease Research Center, Biodesign Institute at Arizona State University, Tempe, AZ, USA.

Molecular Psychiatry
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Increasing brain p62 protein levels improved cognitive function in Alzheimer

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • p62 protein is linked to neurodegenerative diseases like Alzheimer's disease (AD).
  • p62 is involved in tau degradation in AD, but its role in amyloid-beta (Aβ) aggregation and clearance is unclear.

Purpose of the Study:

  • To investigate the role of p62 in regulating amyloid-beta (Aβ) aggregation and degradation in Alzheimer's disease (AD).

Main Methods:

  • Gene therapy to increase p62 expression in APP/PS1 mice (an AD model).
  • Assessed cognitive function, Aβ levels, and plaque load.
  • Utilized genetic and pharmacological approaches to investigate the role of autophagy and the LC3-interacting region of p62.

Main Results:

  • Increased brain p62 expression rescued cognitive deficits in AD mice.
  • This cognitive improvement correlated with reduced Aβ levels and plaque burden.
  • p62-mediated Aβ reduction was dependent on enhanced autophagy.

Conclusions:

  • p62 plays a direct role in regulating amyloid-beta (Aβ) turnover in vivo.
  • Enhancing p62 expression and autophagy may represent a therapeutic strategy for Alzheimer's disease (AD).