Related Experiment Video

Updated: Feb 2, 2026

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
06:23

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Published on: October 30, 2018

8.5K

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Tomoharu Kuboyama1

  • 1Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama; kuboyama@inm.u-toyama.ac.jp.

Journal of Visualized Experiments : Jove
|November 20, 2018
PubMed

Insights

Amyloid-beta (Aβ) triggers memory loss in Alzheimer's disease by damaging neurons. Blocking Aβ-induced endocytosis in growth cones prevents this toxicity, offering a new therapeutic target for early Alzheimer's treatment.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) is characterized by memory impairments linked to Amyloid-beta (Aβ) plaques.
  • Current Aβ-targeting therapies often fail to restore memory in patients with existing deficits.
  • The precise source of Aβ toxicity, particularly its early cellular mechanisms, remains unclear.

Purpose of the Study:

  • To investigate the early molecular mechanisms of Aβ toxicity in neuronal growth cones.
  • To identify the cellular source of Aβ-induced axonal degeneration and memory deficits.
  • To develop a novel protocol for studying early Aβ effects in cultured neurons.

Main Methods:

  • Utilized a novel protocol combining microscopy, gene transfection, and live cell imaging.
  • Examined early changes in axonal growth cones of cultured neurons exposed to Aβ.
  • Investigated the role of endocytosis in Aβ-induced neurotoxicity.

Main Results:

  • Amyloid-beta (Aβ) was found to induce clathrin-mediated endocytosis in axonal growth cones.
  • This Aβ-induced endocytosis led to subsequent growth cone collapse.
  • Inhibition of endocytosis effectively prevented Aβ-induced toxicity in neurons.

Conclusions:

  • Aβ toxicity in Alzheimer's disease originates from its induction of endocytosis in axonal growth cones.
  • Blocking this early endocytic pathway presents a promising strategy for preventative or early-stage AD treatment.
  • The developed protocol offers a valuable tool for studying early Aβ pathogenesis and evaluating novel therapeutic interventions.

More Related Videos

In Situ Visualization of Axon Growth and Growth Cone Dynamics in Acute Ex Vivo Embryonic Brain Slice Cultures10:45

In Situ Visualization of Axon Growth and Growth Cone Dynamics in Acute Ex Vivo Embryonic Brain Slice Cultures

Published on: October 14, 2021

4.1K
Axon Stretch Growth: The Mechanotransduction of Neuronal Growth11:46

Axon Stretch Growth: The Mechanotransduction of Neuronal Growth

Published on: August 10, 2011

17.7K

Related Concept Videos

Neurons: The Axon01:21

Neurons: The Axon

Axons are long, cytoplasmic processes of nerve cells capable of propagating electrical impulses known as action potentials. The cytoplasm or axoplasm of an axon contains neurofibrils, neurotubules, small vesicles, lysosomes, mitochondria, and various enzymes, all encased within the axolemma, the plasma membrane of the axon.
The axon attaches to the cell body at a cone-shaped elevation called the axon hillock. The initial part of the axon, closest to the hillock, is known as the initial segment....
7.3K
Amyloid Fibrils03:03

Amyloid 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,...
11.9K
Amyloid Fibrils03:03

Amyloid Fibrils

6.4K
Population Growth00:57

Population Growth

Population size is dynamic, increasing with birth rates and immigration, and decreasing with death rates and emigration. In ideal conditions with unlimited resources, populations can increase exponentially, which plots as a J-shaped growth rate curve of population size against time. This type of curve is characteristic of newly-introduced invasive species, or populations that have suffered catastrophic declines and are rebounding.
28.6K
Buffer Effectiveness02:19

Buffer Effectiveness

Buffer solutions do not have an unlimited capacity to keep the pH relatively constant . Instead, the ability of a buffer solution to resist changes in pH relies on the presence of appreciable amounts of its conjugate weak acid-base pair. When enough strong acid or base is added to substantially lower the concentration of either member of the buffer pair, the buffering action within the solution is compromised.
The buffer capacity is the amount of acid or base that can be added to a given volume...
55.2K
Meristems and Plant Growth02:36

Meristems and Plant Growth

Plants grow throughout their lives; this is called indeterminate growth, and it distinguishes plants from most animals. Although certain parts of plants stop growing (e.g., leaves and flowers), others grow continuously—like roots and stems.
49.5K