Abstract:An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the b cell of the pancreas, spinal cord and… Show more
“…Conformational studies have helped in further understanding the complexes formed between partial agonists such as MK-8666 and Ago-PAM and the intracellular loops and helixes of FFA1, helping further elucidate agonist binding with this receptor [153]. Stimulation of FFA1 with nonspecific agonists such as DHA or agonists such as GW9508, administered by intracerebroventricular (ICV) infusion, attenuated inflammatory pain induced by formalin and increased the release of β-endorphins [154].…”
Section: O3fa and Free Fatty Acid Receptors (Ffar)mentioning
:
Neurodegenerative disorders are commonly associated with a complex pattern of pathophysiological
hallmarks, including increased oxidative stress and neuroinflammation, which makes
their treatment challenging. Omega-3 Fatty Acids (O3FA) are natural products with reported neuroprotective,
anti-inflammatory, and antioxidant effects. These effects have been attributed to their incorporation
into neuronal membranes or through the activation of intracellular or recently discovered
cell-surface receptors (i.e., Free-Fatty Acid Receptors; FFAR). Molecular docking studies have investigated
the roles of O3FA as agonists of FFAR and have led to the development of receptor-specific
targeted agonists for therapeutic purposes. Moreover, novel formulation strategies for targeted delivery
of O3FA to the brain have supported their development as therapeutics for neurodegenerative disorders.
Despite the compelling evidence of the beneficial effects of O3FA for several neuroprotective
functions, they are currently only available as unregulated dietary supplements, with only a single
FDA-approved prescription product, indicated for triglyceride reduction. This review highlights the
relative safety and efficacy of O3FA, their drug-like properties, and their capacity to be formulated in
clinically viable drug delivery systems. Interestingly, the presence of cardiac conditions such as hypertriglyceridemia
is associated with brain pathophysiological hallmarks of neurodegeneration, such as
neuroinflammation, thereby further suggesting potential therapeutic roles of O3FA for neurodegenerative
disorders. Taken together, this review article summarizes and integrates the compelling evidence
regarding the feasibility of developing O3FA and their synthetic derivatives as potential drugs for neurodegenerative
disorders.
“…Conformational studies have helped in further understanding the complexes formed between partial agonists such as MK-8666 and Ago-PAM and the intracellular loops and helixes of FFA1, helping further elucidate agonist binding with this receptor [153]. Stimulation of FFA1 with nonspecific agonists such as DHA or agonists such as GW9508, administered by intracerebroventricular (ICV) infusion, attenuated inflammatory pain induced by formalin and increased the release of β-endorphins [154].…”
Section: O3fa and Free Fatty Acid Receptors (Ffar)mentioning
:
Neurodegenerative disorders are commonly associated with a complex pattern of pathophysiological
hallmarks, including increased oxidative stress and neuroinflammation, which makes
their treatment challenging. Omega-3 Fatty Acids (O3FA) are natural products with reported neuroprotective,
anti-inflammatory, and antioxidant effects. These effects have been attributed to their incorporation
into neuronal membranes or through the activation of intracellular or recently discovered
cell-surface receptors (i.e., Free-Fatty Acid Receptors; FFAR). Molecular docking studies have investigated
the roles of O3FA as agonists of FFAR and have led to the development of receptor-specific
targeted agonists for therapeutic purposes. Moreover, novel formulation strategies for targeted delivery
of O3FA to the brain have supported their development as therapeutics for neurodegenerative disorders.
Despite the compelling evidence of the beneficial effects of O3FA for several neuroprotective
functions, they are currently only available as unregulated dietary supplements, with only a single
FDA-approved prescription product, indicated for triglyceride reduction. This review highlights the
relative safety and efficacy of O3FA, their drug-like properties, and their capacity to be formulated in
clinically viable drug delivery systems. Interestingly, the presence of cardiac conditions such as hypertriglyceridemia
is associated with brain pathophysiological hallmarks of neurodegeneration, such as
neuroinflammation, thereby further suggesting potential therapeutic roles of O3FA for neurodegenerative
disorders. Taken together, this review article summarizes and integrates the compelling evidence
regarding the feasibility of developing O3FA and their synthetic derivatives as potential drugs for neurodegenerative
disorders.
“…GPR40 is primarily expressed by the pancreatic β-cells, where it plays a pivotal role in FFA-mediated insulin secretion ( 249 ) but also in α-cells ( 78 , 250 ), CCK ( 80 ), GIP ( 251 ), and GLP-1 ( 79 ) producing cells in the gut and in hypothalamic neurons ( 248 , 252 , 253 ). Animals deficient for this receptor are protected from obesity-induced hepatic steatosis, hyperinsulinemia, hypertriglyceridemia and hyperglycaemia.…”
Section: Long and Middle Chain Fatty Acid Receptorsmentioning
An aging world population exposed to a sedentary life style is currently plagued by chronic metabolic diseases, such as type-2 diabetes, that are spreading worldwide at an unprecedented rate. One of the most promising pharmacological approaches for the management of type 2 diabetes takes advantage of the peptide hormone glucagon-like peptide-1 (GLP-1) under the form of protease resistant mimetics, and DPP-IV inhibitors. Despite the improved quality of life, long-term treatments with these new classes of drugs are riddled with serious and life-threatening side-effects, with no overall cure of the disease. New evidence is shedding more light over the complex physiology of GLP-1 in health and metabolic diseases. Herein, we discuss the most recent advancements in the biology of gut receptors known to induce the secretion of GLP-1, to bridge the multiple gaps into our understanding of its physiology and pathology.
“…Conjugated linolenic acid (CLA) is a member of the linolenic acid family that is used as a dietary supplement and has various benefits. CLA was noted more than an anticancer but has other important biological activities (Nakamoto, 2017;Tsuduki, 2015).…”
Electrospun nanofibrous scaffolds show huge potential to improve the neurological outcome in central nervous system disorders. In this study, we cultured mouse embryonic stem cells (mESCs) on an electrospun nanofibrous polylactic acid/ Chitosan/Wax (PLA/CS/Wax) scaffold and surveyed the attachment, behavior, and differentiation of mESCs into neural cells. Differentiation in neural-like cells (NLCs) was investigated with a medium containing SB431542 as a small molecule and conjugated linolenic acid after 20 days. We used Immunocytochemistry and quantitative real-time polymerase chain reaction (RT-PCR) techniques to assess neural marker expression in differentiated cells. SEM imaging demonstrated that mESCs could strongly attach, stretch, and differentiate on PLA/CS/Wax scaffolds. MESCs that were cultured on PLA/CS/Wax scaffolds showed enhanced numbers of neural structures and neural markers including Nestin, NF-H, Tuj-1, and Map2 in neural induction medium compared to the control sample. These results revealed that electrospun PLA/CS/Wax scaffolds associated with the induction medium can assemble proper conditions for stem cell differentiation into NLCs. We hope that the development of new technologies in neural tissue engineering may pave a new avenue for neural tissue regeneration. K E Y W O R D S beeswax, electrospun nanofibrous scaffolds, mESCs, neural differentiation, small molecule
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