HMGB1 in Amyloid-Beta Pathology: Mechanistic Insights and Therapeutic Implications for Alzheimer's Disease
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Updated: Oct 17, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Song-I Seol1, Ji-Eun Kim2, Dashdulam Davaanyam1
1Department of Anatomy, Inha University School of Medicine, Incheon 22212, Republic of Korea.
Abstract:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. Beyond these hallmark pathological features, the complex pathogenesis of AD involves cellular dysfunctions associated with chronic oxidative stress and neuroinflammation. Central to these inflammatory pathways is the extracellular release of the nuclear protein high-mobility group box 1 (HMGB1) from neurons and microglia. Extracellular HMGB1 disrupts homeostatic and reparative microglial functions, impairing the phagocytic clearance of amyloid-beta and driving neuroinflammation to accelerate AD pathogenesis. Consequently, targeting HMGB1 offers a promising therapeutic strategy for AD. This review examines recent progress and key insights regarding HMGB1-associated neuroinflammatory pathology in AD. We evaluate its regulation across transcriptional upregulation, cellular redistribution, age-related alterations, and Aβ-associated pathology. We further detail the pleiotropic effects of extracellular HMGB1, including neuroinflammation, defective Aβ phagocytic clearance, and genomic instability. Finally, we discuss the potential clinical utility of targeting HMGB1 to mitigate AD progression and provide HMGB1-related perspectives for future studies.
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