(fatty acid crucial to brain/muscle function and inflammation)
Inflammatory and mitogenic signaling molecules
12-Lipoxygenase (12-LOX) is expressed on platelets and in the pancreas. The 12-LOX lipid products of arachidonic acid (12-oxylipins) lead to oxidative and endoplasmic reticulum (ER) stress and macrophage activation.
12-Lipoxygenase is a key driver behind platelet activation. Regulation of platelet activation is essential for the prevention and treatment of cardiovascular atherothrombotic events. Interestingly, inhibition of 12 LOX decreases thrombosis without impairing hemostasis.
In Type 1 Diabetes, 12-LOX uniquely drives both the innate and the adaptive immune mediated beta islet cell destruction. Knockout 12LOX mice are completely protected against the development of T1D. The selective inhibition of of 12LOX prevents the progression of T1D and rescues beta islet cell function in both mice and human models
In stroke, the enzyme 15-lipoxygenase (15-LOX) is a key driver of secondary brain damage, promoting oxidative stress, neuronal death, blood-brain barrier breakdown, and edema in the penumbra (salvageable tissue) by damaging mitochondria.
•Oxidative Stress & Mitochondrial Damage: ALOX15 generates reactive oxygen species (ROS) and directly damages neuronal mitochondria, triggering cell death pathways.
•Neuronal Death: It acts as a central executor in oxidative stress-related neuronal death, particularly in the vulnerable penumbra, leading to delayed cell death.
•Blood-Brain Barrier (BBB) Weakening: Increased ALOX15 activity contributes to BBB disruption, worsening edema and overall injury.
•Neuroinflammation: It promotes inflammatory lipid mediators and pathways, exacerbating tissue damage after the initial ischemic event.
