Related Experiment Video
Updated: May 2, 2026
07:55
Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
10.7K
UV irradiation accelerates amyloid precursor protein (APP) processing and disrupts APP axonal transport
Angels Almenar-Queralt1, Tomas L Falzone, Zhouxin Shen
1Department of Cellular and Molecular Medicine, Department of Neurosciences, School of Medicine, Department of Pharmacology and Neurosciences, and Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, and Sanford Consortium for Regenerative Medicine, La Jolla, California 92037.
Summary
Neuronal damage accelerates amyloid precursor protein (APP) processing, impairing axonal transport and potentially causing synaptic failure. This study reveals a novel mechanism linking cellular damage to neurodegenerative disease pathways like Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Amyloid precursor protein (APP) processing is implicated in Alzheimer's disease (AD).
- Mechanisms regulating APP levels, processing, and consequences of altered processing remain unclear.
- Understanding APP's role in neuronal health and disease is crucial.
Purpose of the Study:
- Investigate the impact of neuronal damage on APP processing and axonal transport.
- Elucidate the molecular mechanisms and cellular compartments involved in damage-induced APP processing.
- Identify the functional consequences of impaired APP axonal transport.
Main Methods:
- Utilized mouse and human cell models.
- Induced neuronal damage using UV irradiation.
- Employed pharmacological inhibition of endosomal/lysosomal pathways.
- Analyzed APP-containing axonal transport vesicles via electron microscopy, biochemistry, and mass spectrometry.
Main Results:
- UV irradiation accelerated secretase-dependent processing of APP, APLP1, and APLP2 in neuronal cells.
- Endosomal/lysosomal inhibition partially protected against UV-induced APP processing.
- Damage-induced APP processing impaired axonal transport of APP.
- Identified APP-containing vesicles with secretase machinery, motors, and disease-associated proteins.
Conclusions:
- Neuronal damage triggers accelerated APP processing, involving endosomal/lysosomal pathways.
- Impaired APP axonal transport is a consequence of damage-induced processing.
- APP vesicle cargo suggests a link between impaired transport and neuronal dysfunction/neurodegeneration.
- Findings offer insights into AD pathogenesis and synaptic maintenance failure.
Related Concept Videos
01:29Alzheimer Disease l: Introduction
21
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
21
01:37The Unfolded Protein Response
5.6K
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...
5.6K
01:35Mutations
31.2K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
31.2K
03:03Amyloid Fibrils
10.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
10.2K
03:03Amyloid Fibrils
5.2K
5.2K
01:23Alzheimer Disease ll: Pathophysiology
35
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
35