Recent studies have provide significant insights into the role of High Mobility Group Box 1 (HMGB1) in Alzheimer’s disease (AD), particularly its involvement in neuroinflammation and cognitive decline.
As highlighted during Alzheimer’s & Brain Awareness Month, AD continues to pose significant challenges in the realm of neurodegenerative diseases, particularly with its increasing prevalence among the aging population
Pyroptosis and Blood-Brain Barrier Breakdown:
Diabetes mellitus, a known risk factor for dementia, is linked to blood-brain barrier (BBB) breakdown, which contributes to cognitive decline. HMGB1, when released from the nucleus, activates the NLRP3 inflammasome, triggering pyroptosis and subsequent BBB dysfunction. This pathway is crucial in diabetes-associated cognitive decline, suggesting that targeting HMGB1 could be a promising therapeutic approach for preventing dementia in diabetic patients.
Neuroinflammatory Pathways and Dementia Severity:
In AD patients, serum levels of HMGB1, along with Sirtuin-1 (SIRT-1), Toll-Like Receptor-4 (TLR4), and Interleukin-6 (IL-6), are significantly elevated. These biomarkers are associated with the severity of dementia, underscoring the role of HMGB1 in neuroinflammation and neuronal loss. By interacting with TLR4 and activating downstream pathways like NF-κB, HMGB1 perpetuates neuroinflammation, leading to neuronal loss and cognitive impairment. This highlights its potential as a biomarker for early AD diagnosis and monitoring disease progression.
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Read the full articles about the studies:
https://pubmed.ncbi.nlm.nih.gov/34844084/
https://pubmed.ncbi.nlm.nih.gov/36573053/
