br Conclusion br Acknowledgement This study was supported by

Conclusion
Acknowledgement This study was supported by NIH/NINDSR01 NS036812-16.
Introduction Lipoxygenases (LOXs) are a heterogeneous family of enzymes that catalyze the peroxidation of polyunsaturated fatty acids (PUFAs). By oxidizing free PUFAs, they were shown to contribute to the generation of various bioactive lipid mediators. However, LOX-mediated oxidation of PUFAs esterified to phospholipids can also generate oxidized phospholipids that induce alternative signaling pathways and additionally affect the biophysical properties of cellular membranes. Different LOXs were shown to exert both pro- and anti-inflammatory effects, regulate phagocytosis and autophagy, control barrier function and modulate coagulation and hemostasis. Human 15-lipoxygenase (15-LOX) type 1 and it's murine orthologue 12/15-lipoxygenase (12/15-LOX) are encoded by the ALOX15 gene and represent evolutionary highly conserved members of this family of enzymes that are primarily expressed in myeloid cisapride such as reticulocytes, eosinophils and macrophages. Although the biological properties of 15-LOX and 12/15-LOX have been the focus of intense research, these efforts yielded conflicting results. The same is true for the various enzymatic products generated by 12/15-LOX, like hydroxyeicosatetraenoic acids (HETEs). 12/15-LOX and 15-LOX have been implicated in the pathogenesis of various inflammatory, metabolic, neurodegenerative and infectious disorders. The physiologic function of these two enzymes has remained still incompletely understood, though [1]. This review aims to give an overview about the biological properties of 12/15-LOX and 15-LOX and to give specific insights into their role during inflammation and immunity.
Products and properties of 12/15-lipoxygenase
12/15 Lipoxygenase during the resolution of inflammation and regulation of the innate and adaptive immune response
12/15-LOX during the pathophysiology of disease
Concluding remarks As an important regulator of inflammation, 12/15-LOX might be a relevant future target for clinical purposes. On the one hand, 12/15-LOX-inhibitors such as PD146176 [12] could provide potent therapeutics against a number of 12/15-LOX-triggered diseases, which include diabetes, hypertension and other disorders linked to chronic adipose tissue inflammation [10]. The emerging knowledge on the anti-inflammatory role of distinct 12/15-LOX-derived mediators such as lipoxins, on the other hand, suggests that lipoxin analogues and ALX agonists as well as 12/15-LOX activators could help to foster the resolution of inflammation and thus represent interesting molecules for the future therapy of chronic inflammatory diseases such as rheumatoid arthritis [167].
Acknowledgments This work was supported by the Deutsche Forschungsgemeinschaft (CRC1181 to G.K.), the Else Kröner Fresenius Stiftung (2013_A274 to G.K.) and the European Union (ERC StG 640087 – SOS to G.K.).
Introduction Stroke is the leading cause of disability and the fifth leading cause of death in the United States (Writing Group et al., 2016). On average, every 4 min a human dies of stroke (Lackland et al., 2014, Mozaffarian etal., 2016). Together with cardiovascular diseases, its economic burden is higher than the other diagnostic groups including cancer. The annual direct and indirect cost of cardiovascular diseases and stroke is an estimated $316.6 billion in the United States (Writing Group et al., 2016). Despite these catastrophic effects of stroke, the only FDA-approved drug treatment option for acute stroke is the application of tissue plasminogen activator (tPA) which has many drawbacks including the narrow time window, low rate of reachable patients, and severe side effects including hemorrhage (Kaur et al., 2004, Lees et al., 2010, National Institute of Neurological Disorders and stroke rt-PA Stroke Study Group, 1995, Wang et al., 2004, Yepes et al., 2009). New treatment options are thus of great interest in stroke management, and screening for novel drugs in animal models is an important drug development approach. Besides STAIR advices to use different animal stroke models both permanent and transient and also with reperfusion and with thrombolysis (Fisher et al., 2009). The great majority of ischemic strokes are due to an occlusion in a cerebral artery by a thrombus especially in the middle cerebral artery (MCA) in human (Hossmann, 2012). So it is feasible to choose a model that mimics human stroke like FeCl3-induced MCA occlusion model to test novel drugs (Denorme et al., 2016). Stroke damages the neurovascular unit, causes massive cell death and activates several oxidative stress-related pathways like lipid peroxidation, during its acute phase (Hardingham and Lipton, 2011, Lo et al., 2003, Lo et al., 2005, Moskowitz et al., 2010, Niizuma et al., 2009). Lipoxygenases play one of the major roles in stroke related oxidative stress. Especially 12/15-lipoxygenase, the dominant isoform in the brain, is increased in neurons and endothelial cells in the peri-infarct area, contributing to delayed cell death in the penumbra, weakening of the blood–brain barrier, and resulting in edema formation (Jin et al., 2008, van Leyen et al., 1998, van Leyen et al., 2006, van Leyen et al., 2014). Therefore, lipoxygenase inhibitors are in scope of acute stroke treatment research, and among them LOX Block-1 (LB-1) is a new candidate considering its potential (Yigitkanli et al., 2013).