Unveiling the Neuroprotective Effect of Paraoxonase 1 in Neurodegenerative Diseases Focusing on Alzheimer's Disease.

PMID 41335160 | DOI 10.1007/s12035-025-05493-1 · Molecular neurobiology · 2025 · View on PubMed ↗

Paraoxonase 1 (PON1) is a hydrolyzing paraoxon enzyme; it prevents the development of oxidative stress damage. PON1 primarily binds to high-density lipoprotein (HDL). Although PON1 is not directly expressed in the brain, it crosses the blood-brain barrier (BBB) via HDL, potentially exerting neuroprotective effects. It has been shown that the reduction of PON1 activity is associated with the development and progression of Alzheimer's disease (AD) and other neurodegenerative diseases by inducing oxidative stress and neuroinflammation. Despite these findings, the exact role of PON1 in AD and other neurodegenerative diseases is not fully elucidated. Therefore, the aim of the present review was to discuss and explain the precise role of PON1 in AD, and how PON1 activators could be effective in the management of AD. Clinical trial: not applicable.