The 12‐15‐lipoxygenase is a modulator of Alzheimer's‐related tau pathology <i>in vivo</i>

Giannopoulos, Phillip F.; Joshi, Yash B.; Chu, Jin; Praticò, Domenico

doi:10.1111/acel.12136

Cited by 40 publications

(31 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most notably, activation of these enzymes has been linked to the progression of AD neuropathology. The expression of LOX enzymes is increased in human AD brains, and genetic or pharmacological approaches to block 5-LOX, 12/15-LOX, and other components of LOX cascade in AD transgenic mice significantly reduce Aβ and tau pathology, and restore cognition [31–36]. Together, these data suggest that an inhibition of LOX activity is beneficial in the treatment and prevention of AD.…”

Section: Discussionmentioning

confidence: 99%

Restoration of Lipoxin A4 Signaling Reduces Alzheimer's Disease-Like Pathology in the 3xTg-AD Mouse Model

Dunn

Ager

Baglietto‐Vargas

et al. 2014

JAD

View full text Add to dashboard Cite

The initiation of an inflammatory response is critical to the survival of an organism. However, when inflammation fails to reach resolution, a chronic inflammatory state may occur, potentially leading to bystander tissue damage. Accumulating evidence suggests that chronic inflammation contributes to the progression of Alzheimer’s disease (AD), and identifying mechanisms to resolve the pro-inflammatory environment stimulated by AD pathology remains an area of active investigation. Previously, we found that treatment with the pro-resolving mediator aspirin-triggered lipoxin A4 (ATL), improved cognition, reduced Aβ levels, and enhanced microglia phagocytic activity in Tg2576 transgenic AD mice. Here, we evaluated the effect of aging on brain lipoxin A4 (LXA4) levels using non-transgenic and 3xTg-AD mice. Additionally, we investigated the effect of ATL treatment on tau pathology in 3xTg-AD mice. We found that LXA4 levels are reduced with age, a pattern significantly more impacted in 3xTg-AD mice. Moreover, ATL delivery enhanced the cognitive performance of 3xTg-AD mice, reduced Aβ levels, as well as decreased the levels of phosphorylated-tau (p-tau). The decrease in p-tau was due in part to an inhibition of the tau kinases GSK-3β and p38 MAPK. In addition, microglial and astrocyte reactivity was inhibited by ATL treatment. Our results suggest that the inability to resolve the immune response during aging might be an important feature that contributes to AD pathology and cognitive deficits. Furthermore, we demonstrate that activation of LXA4 signaling could serve as a potential therapeutic target for AD related inflammation and cognitive dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Restoration of Lipoxin A4 Signaling Reduces Alzheimer's Disease-Like Pathology in the 3xTg-AD Mouse Model

Dunn

Ager

Baglietto‐Vargas

et al. 2014

JAD

View full text Add to dashboard Cite

show abstract

“…Besides these, other cytokines (IL-1β, IL-6, IL-23), growth factors (TGF-β), inflammatory mediators (signal transducer and activator of transcription (STAT)-3, toll-like receptor (TLR)-2) and genetic factors (coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR), vitamin D receptor (VDR)) significantly accelerate the inflammatory processes in psoriasis (Honma et al 2012;Tiala et al 2007). 15-Lipoxygenase (15-LOX) enzyme in humans is known to be involved in the production of leukotrienes that act as proinflammatory products, giving rise to allergic reactions (Brash et al 1997;Vanderhoek and Bailey 1984), thereby responsible for pathogenesis of many inflammatory disorders, including rheumatoid arthritis, Alzheimer's dementia and psoriasis (Giannopoulos et al 2013;Gheorghe et al 2009). 15-LOX-2 has been implicated in IFN-γ-induced inflammatory processes in psoriatic skin (Setsu et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of imiquimod-induced psoriasis-like dermatitis in mice by herbal extracts from some Indian medicinal plants

2015

View full text Add to dashboard Cite

Psoriasis is a chronic autoimmune human skin disorder that is characterized by excessive proliferation of keratinocytes, scaly plaques, severe inflammation and erythema. The pathophysiology of psoriasis involves interplay between epidermal keratinocytes, T lymphocytes, leukocytes and vascular endothelium. Increased leukocyte recruitment and elevated levels of cytokines, growth factors and genetic factors like interleukin (IL)-1β, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2, coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR) and vitamin D receptor (VDR) are the most critical factors governing the exacerbation of psoriasis. In the present study, an attempt was made to elucidate the preventive role of herbal extracts of four dermo-protective Ayurvedic plants, Tinospora cordifolia (TC), Curcuma longa (CL), Celastrus paniculatus (CP) and Aloe vera (AV), against psoriasis-like dermatitis. Parkes (P) strain mice were initially induced with psoriasis-like dermatitis using topical application of imiquimod (IMQ, 5 %), followed by subsequent treatment with the herbal extracts to examine their curative effect on the psoriasis-like dermatitis-induced mice. The extracts were orally/topically administered to mice according to their ED/LD50 doses. Phenotypical observations, histological examinations, and semi-quantitative reverse transcription PCR (RT-PCR) analyses of the skin and blood samples of the control, IMQ-treated and herbal extract-treated psoriasis-like dermatitis-induced mice lead to the conclusion that the combination extract from all the plants was instrumental in downregulating the overexpressed cytokines, which was followed by the CL extract. Moreover, lesser yet positive response was evident from CP and TC extracts. The results suggest that these plants can prove to have tremendous preventive potential against the disease and can open the way to new therapeutic strategies for psoriasis treatment.

show abstract

“…Lower expression levels have been reported for polymorphonuclear leukocytes [70,71], alveolar macrophages [72], vascular cells [73], uterus [74], various parts of the brain [75,76] and for atherosclerotic lesions [77]. Human peripheral blood monocytes do not express ALOX15.…”

Section: Human Alox15mentioning

confidence: 99%

Catalytic Multiplicity of 15-Lipoxygenase-1 Orthologs (ALOX15) of Different Species

Kühn

Karst

Heydeck

2016

Lipoxygenases in Inflammation

View full text Add to dashboard Cite

Lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which have been implicated in a number of physiological processes and in the pathogenesis of inflammatory, hyperproliferative and neurodegenerative diseases. They occur in bacteria and eucarya and the human genome involves six functional LOX genes, which encode for six different LOX isoforms. One of these isoforms is ALOX15, which has first been described in rabbits in 1974 as an enzyme capable of oxidizing membrane phospholipids during the maturational breakdown of mitochondria in immature red blood cells. During the following decades ALOX15 orthologs have extensively been characterized and their biological functions have been studied in a number of cellular in vitro systems as well as in various whole animal disease models. This review is aimed at summarizing the current knowledge on the protein-chemical, molecular biological and enzymatic properties of ALOX15 orthologs of various mammalian species (rabbit, pig, human, nonhuman primates, mouse, rat). Because of space limitations the biological roles of ALOX15 orthologs have not been addressed since this topic has extensively been covered in a previous review (Kuhn et al., Biochim Biophys Acta 1851:308-330, 2015.

show abstract

The 12‐15‐lipoxygenase is a modulator of Alzheimer's‐related tau pathology in vivo

Cited by 40 publications

References 27 publications

Restoration of Lipoxin A4 Signaling Reduces Alzheimer's Disease-Like Pathology in the 3xTg-AD Mouse Model

Restoration of Lipoxin A4 Signaling Reduces Alzheimer's Disease-Like Pathology in the 3xTg-AD Mouse Model

Inhibition of imiquimod-induced psoriasis-like dermatitis in mice by herbal extracts from some Indian medicinal plants

Catalytic Multiplicity of 15-Lipoxygenase-1 Orthologs (ALOX15) of Different Species

Contact Info

Product

Resources

About