TY  - EJOU
AU  - Hoxha, Malvina 
AU  - Tricarico, Domenico 
AU  - Capobianco, Loredana 

TI  - Arachidonic Acid Mediators and Nrf2 in Neurodegenerative Diseases
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - Arachidonic acid (AA) and its mediators, including prostaglandins (PGs) and lipoxygenase (LOX) products, have different and sometimes opposing effects on neuronal survival and inflammatory signaling. Evidence indicates a functional and dynamic interaction between AA-derived lipid mediators and the nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant and cytoprotective responses. Certain AA metabolites, such as the cyclopentenone prostaglandin 15-deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> (15d-PGJ<sub>2</sub>) and LOX-derived products including 5-oxo-eicosatetraenoic acid (5-oxo-ETE), have been shown to activate Nrf2 signaling. This activation enhances antioxidant defenses, promotes redox homeostasis, and mitigates inflammatory responses in neuronal and glial cells. In contrast, other AA metabolites contribute to sustained neuroinflammation and cytotoxicity, highlighting the dual and context-dependent role of AA signaling in the central nervous system. This duality positions AA mediators as both drivers of pathology and modulators of endogenous protective pathways. Pharmacological strategies targeting cyclooxygenase (COX) enzymes or downstream prostaglandin signaling have therefore been explored for neuroprotective potential; however, clinical translation has been limited by the complex functions of COX-derived products. Arachidonic acid-derived mediators regulating Nrf2 may offer anti-inflammatory yet protective strategies.
KW  - Arachidonic acid pathway; neurodegenerative diseases; nuclear factor erythroid 2-related factor 2; prostaglandins

DO  - 10.32604/biocell.2026.080846