Related Experiment Video
Updated: Aug 21, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
High mobility group box protein-1 inhibits microglial Abeta clearance and enhances Abeta neurotoxicity
Kazuyuki Takata1, Yoshihisa Kitamura, Daiju Tsuchiya
1Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Abstract:
One pathogenic characteristic of Alzheimer's disease (AD) is the formation of extracellular senile plaques with accumulated microglia. According to the amyloid hypothesis, the increase or accumulation of amyloid-beta (Abeta) peptides in the brain parenchyma is the primary event that influences AD pathology. Although the role of microglia in AD pathology has not been clarified, their involvement in Abeta clearance has been noted. High mobility group box protein-1 (HMGB1) is an abundant nonhistone chromosomal protein. We reported recently that HMGB1 was associated with senile plaques and the total protein level significantly increased in AD brain. In this study, diffuse HMGB1 immunoreactivity was observed around dying neurons in the kainic acid- and Abeta1-42 (Abeta42)-injected rat hippocampi. HMGB1 also colocalized with Abeta in the Abeta42-injected rats but not in transgenic mice, which show massive Abeta production without neuronal loss in their brains. Furthermore, coinjection of HMGB1 delayed the clearance of Abeta42 and accelerated neurodegeneration in Abeta42-injected rats. These results suggest that HMGB1 released from dying neurons may inhibit microglial Abeta42 clearance and enhance the neurotoxicity of Abeta42. HMGB1 may thus be another target in the investigation of a therapeutic strategy for AD.
Insights
High mobility group box protein-1 (HMGB1) released from dying neurons may impede microglial clearance of amyloid-beta 42 (Abeta42) and worsen neurotoxicity, suggesting HMGB1 as a therapeutic target for Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Pathology
- Molecular Biology
Background:
- Alzheimer's disease (AD) is characterized by senile plaques and microglial accumulation.
- The amyloid hypothesis posits that amyloid-beta (Abeta) accumulation drives AD pathology.
- Microglia play a role in Abeta clearance, though their exact function in AD is unclear.
Purpose of the Study:
- To investigate the role of High mobility group box protein-1 (HMGB1) in Alzheimer's disease pathology.
- To determine the effect of HMGB1 on Abeta clearance and neurodegeneration.
Main Methods:
- Examined HMGB1 immunoreactivity in rat hippocampi after kainic acid and Abeta1-42 (Abeta42) injection.
- Assessed HMGB1 colocalization with Abeta in Abeta42-injected rats and transgenic mice.
- Investigated the impact of coinjected HMGB1 on Abeta42 clearance and neurodegeneration in rats.
Main Results:
- Diffuse HMGB1 immunoreactivity was observed around dying neurons in rat hippocampi.
- HMGB1 colocalized with Abeta in Abeta42-injected rats, but not in transgenic mice lacking neuronal loss.
- Coinjection of HMGB1 delayed Abeta42 clearance and accelerated neurodegeneration in rats.
Conclusions:
- HMGB1 released from dying neurons may inhibit microglial Abeta42 clearance.
- HMGB1 may enhance Abeta42 neurotoxicity, contributing to Alzheimer's disease pathogenesis.
- HMGB1 represents a potential therapeutic target for Alzheimer's disease.
