Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε in an ex vivo murine model of brain ischemia

Rahman, S M Khaledur; Hussain, Zahir; Morito, Katsuya; Takahashi, Naoko; Sikder, Mohammad Mamun; Tanaka, Tamotsu; Ohta, Kenichi; Ueno, Masaki; Takahashi, Hiroo; Yamamoto, Tohru; Murakami, Makoto; Uyama, Toru; Ueda, Natsuo

doi:10.1016/j.bbalip.2022.159222

Cited by 3 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding NAPE production, a specific PLA (cytosolic PLA2ε) has recently been identified as a likely candidate for catalysing this reaction. However, recent models of cPLA2ε KO do not show significant decreases in brain NAPE or AEA levels and evidence-significant off-target reactions [289,290]. The controversial results from these models indicate that several as-of-yet uncharacterised pathways contribute to AEA tone, highlighting the functional redundancy in NAE biosynthetic pathways.…”

Section: Aea Synthesis and Catabolismmentioning

confidence: 97%

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Kouchaeknejad,

Van Der Walt,

De Donato

et al. 2023

IJMS

View full text Add to dashboard Cite

As central nervous system (CNS)-related disorders present an increasing cause of global morbidity, mortality, and high pressure on our healthcare system, there is an urgent need for new insights and treatment options. The endocannabinoid system (ECS) is a critical network of endogenous compounds, receptors, and enzymes that contribute to CNS development and regulation. Given its multifaceted involvement in neurobiology and its significance in various CNS disorders, the ECS as a whole is considered a promising therapeutic target. Despite significant advances in our understanding of the ECS’s role in the CNS, its complex architecture and extensive crosstalk with other biological systems present challenges for research and clinical advancements. To bridge these knowledge gaps and unlock the full therapeutic potential of ECS interventions in CNS-related disorders, a plethora of molecular–genetic tools have been developed in recent years. Here, we review some of the most impactful tools for investigating the neurological aspects of the ECS. We first provide a brief introduction to the ECS components, including cannabinoid receptors, endocannabinoids, and metabolic enzymes, emphasizing their complexity. This is followed by an exploration of cutting-edge imaging tools and genetic models aimed at elucidating the roles of these principal ECS components. Special emphasis is placed on their relevance in the context of CNS and its associated disorders.

show abstract

Section: Aea Synthesis and Catabolismmentioning

confidence: 97%

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Kouchaeknejad,

Van Der Walt,

De Donato

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Since for N-acylation of phosphatidylethanolamine cPLA 2ε selectively abstracts an acyl chain from the sn-1 position of the glycerol backbone of glycerophospholipid, which is abundant in saturated and mono-unsaturated fatty acids rather than poly-unsaturated fatty acids like AA, Narachidonoyl-phosphatidylethanolamine and AEA account for a small percentage of the N-acylphosphatidylethanolamine (NAPE) and fatty acid ethanolamides present in cells. The analysis of cPLA 2εdeficient mice revealed the central role of this enzyme in the accumulation of NAPEs and Nacylethanolamines in an imiquimod-induced psoriasis model (Liang et al, 2022), as well as in an ex vivo model of brain ischemia (Rahman et al, 2022). The NAPE-forming activity of cPLA 2ε in skin was suggested to be protective against skin inflammation such as psoriasis by producing anti-inflammatory Nacylethanolamines.…”

Section: A Enzymes Of Aea Productionmentioning

confidence: 99%

Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years

et al. 2023

Self Cite

View full text Add to dashboard Cite

The cannabis derivative marijuana is the most widely used recreational drug in the Western world, that is consumed by an estimated 83 million individuals (~3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the USA and worldwide. Compelling research evidence and the FDA cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ 9tetrahydrocannabinol (THC) and other plant-derived cannabinoids (phytocannabinoids). Of note, our body has a complex endocannabinoid system (ECS) -made of receptors, metabolic enzymes and transporters -that is also regulated by phytocannabinoids. The first endocannabinoid to be discovered 30 years ago was anandamide (N-arachidonoyl-ethanolamine); since then, distinct elements of ECS have been the target of drug design programs aimed at curing (or at least slowing down) a number of human diseases, both in the central nervous system and at the periphery. Here, a critical review of our knowledge of the goods and bads of ECS as a therapeutic target are presented, in order to define the benefits of ECS-active phytocannabinoids and ECS-oriented synthetic drugs for human health. Significance Statement -The endocannabinoid system plays important roles virtually everywhere in our body and is either involved in mediating key processes of central and peripheral diseases or represents a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of the components of this complex system, and in particular of key receptors (like CB 1 R and CB 2 R) and metabolic enzymes (like FAAH and MAGL), will advance our understanding of endocannabinoid signaling and activity at molecular, cellular, and system levels providing new opportunities to treat patients.

show abstract

Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families

Simard

Archambault

Lavoie

et al. 2022

Biochemical Pharmacology

View full text Add to dashboard Cite

Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε in an ex vivo murine model of brain ischemia

Cited by 3 publications

References 39 publications

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years

Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families

Contact Info

Product

Resources

About