Related Experiment Video
Updated: Jun 13, 2026
10:19
Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps
Published on: August 14, 2016
Endocytic pathways mediating oligomeric Abeta42 neurotoxicity
Chunjiang Yu1, Evelyn Nwabuisi-Heath, Kevin Laxton
1Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612 USA. mladu@uic.edu.
Molecular Neurodegeneration
|May 19, 2010
Summary
Oligomeric amyloid-beta (oAbeta42) causes Alzheimer
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid plaques, primarily composed of amyloid-beta peptide (Abeta).
- Overproduction or reduced clearance of Abeta42 leads to Abeta accumulation and plaque formation.
- Soluble oligomeric Abeta (oAbeta) is a likely proximal cause of AD.
Purpose of the Study:
- To investigate the role of endocytosis in mediating oligomeric Abeta42-induced neurotoxicity and intraneuronal Abeta accumulation.
- To determine the specific endocytic pathways involved in oAbeta42 neurotoxicity.
Main Methods:
- Inhibition of clathrin function using pharmacological inhibitors, knockdown, and dominant-negative mutants.
- Inhibition of dynamin and RhoA using dominant-negative mutants.
- Pharmacological inhibition of dynamin-mediated endocytosis with genistein.
Main Results:
- Inhibition of clathrin did not affect oAbeta42-induced neurotoxicity or Abeta accumulation.
- Inhibition of dynamin and RhoA significantly reduced neurotoxicity and intraneuronal Abeta accumulation.
- Genistein treatment also reduced neurotoxicity, confirming the role of dynamin-mediated endocytosis.
Conclusions:
- Dynamin-mediated and RhoA-regulated endocytosis are critical for oAbeta42-induced neurotoxicity.
- These pathways are integral to the intraneuronal accumulation of Abeta in Alzheimer's disease.
Related Concept Videos
01:32Export of Misfolded Proteins out of the ER
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...
01:23Alzheimer Disease ll: Pathophysiology
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 microglia. Abnormal...
01:00Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
03:03Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:45ER Retrieval Pathway
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...