Sphingosine-1-Phosphate and Rheumatoid Arthritis: Pathological Implications and Potential Therapeutic Targets

Zhang, Zhiyi; Chang, Zhao

doi:10.5772/53308

Cited by 3 publications

(2 citation statements)

References 130 publications

(172 reference statements)

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“…Sphingosine-1-phosphate (S1P) and lysophosphatidic acid, among others, are involved in RASF activation. Alterations in S1P signaling can lead to synovial fibroblast migration, proliferation, survival and production of proinflammatory cytokines/chemokines [ 80 ]. Ablation of autotaxin ATX, a lysophospholipase D that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), in RASFs, resulted in disease attenuation in animal models of arthritis [ 79 ].…”

Section: Metabolic Reprogramming As An Alternative Survival Pathwamentioning

confidence: 99%

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

Aghakhani

Zerrouk

Niarakis

2020

Cancers

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Fibroblasts, the most abundant cells in the connective tissue, are key modulators of the extracellular matrix (ECM) composition. These spindle-shaped cells are capable of synthesizing various extracellular matrix proteins and collagen. They also provide the structural framework (stroma) for tissues and play a pivotal role in the wound healing process. While they are maintainers of the ECM turnover and regulate several physiological processes, they can also undergo transformations responding to certain stimuli and display aggressive phenotypes that contribute to disease pathophysiology. In this review, we focus on the metabolic pathways of glucose and highlight metabolic reprogramming as a critical event that contributes to the transition of fibroblasts from quiescent to activated and aggressive cells. We also cover the emerging evidence that allows us to draw parallels between fibroblasts in autoimmune disorders and more specifically in rheumatoid arthritis and cancer. We link the metabolic changes of fibroblasts to the toxic environment created by the disease condition and discuss how targeting of metabolic reprogramming could be employed in the treatment of such diseases. Lastly, we discuss Systems Biology approaches, and more specifically, computational modeling, as a means to elucidate pathogenetic mechanisms and accelerate the identification of novel therapeutic targets.

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Section: Metabolic Reprogramming As An Alternative Survival Pathwamentioning

confidence: 99%

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

Aghakhani

Zerrouk

Niarakis

2020

Cancers

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“…There have even been investigations into their potential uses for cancer, due to the interference with angiogenesis and autoimmune diabetes, suggesting a wide array of potential applications and a need for further study into S1PR regulations to have the next generation of more selective S1P modulators [60,61,62] (Table 1). …”

Section: Other Potential Applicationsmentioning

confidence: 99%

The sphingosine-1-phosphate receptor: A novel therapeutic target for multiple sclerosis and other autoimmune diseases

Mao-Draayer

Sarazin

Fox

et al. 2017

Clinical Immunology

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Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous system (CNS). Currently, there is no drug that provides a cure for MS. To date, all immunotherapeutic drugs target relapsing remitting MS (RRMS); it remains a daunting medical challenge in MS to develop therapy for secondary progressive MS (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P) receptor modulator FTY720 (fingolimod [Gilenya®]) for RR-MS in 2010, there have been many emerging studies with various selective S1P receptor modulators in other autoimmune conditions. In this article, we will review how S1P receptor may be a promising therapeutic target for SP-MS and other autoimmune diseases such as psoriasis, polymyositis and lupus.

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Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease

Kumar

Singh

Sharma

et al. 2019

CST

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Background: The humans can be affected by more than 100 types of cancers in which about 22 % cancer death are caused by tobacco, 10% due to alcohol and obesity, 5-10 % by genetic defects and 20 % by infections. Rheumatoid arthritis, an autoimmune disorder, occurs mostly in middle age, affects 2.5 times more to females than males and till 2015, more than 24.5 Million people get affected from this disorder. The deaths due to rheumatoid arthritis were 28000 in 1990 and increased to 38000 in 2013. Parkinson’s disease, a neurodegenerative disorder of central nervous system affects about 6.2 million people in 2015 and responsible for approximately 117400 deaths worldwide. Parkinson’s disease occurs mainly over the age of 60 and males get more affected than females. Methods: Bibliographic database has created by mendeley desktop software for available literature in peer reviewed research articles especially by titles and disease names as keywords with AND Boolean operator (title AND year or author AND year). The intervention and findings of quality papers were extracted by detailed study and a conceptual framework has developed. Results: Total 121 research and review articles are cited in this review to produce high impact in literature for pathophysiology and receptors involved in all three diseases. Changes in enzyme action, prohibition of angiogenesis and inhibition of microtubule are the main areas where anticancer molecules may perform significant effect. The immune system is not a good target for rheumatic treatment due to many complications that occur in body but fibroblast, like synoviocytes, proteases which are responsible for cartilage destruction and osteoclast differentiation may be the beneficial targets for pharmacoactive molecules in the treatment of rheumatoid arthritis. In Parkinson’s disease, supply of dopamine to brain from outside results in brain dopamine synthesis decrement which increase drug dependency. The compounds which stimulate secretion, reuptake inhibitor and increment in dopaminergic neurons may be good targets. Conclusion: Alteration of signal transduction by a drug is the goal of chemogenomics, a new branch formed by combination of chemistry and genomics. The proliferation, angiogenesis and apoptosis of cancer cells are regulated by cellular signaling of transcription factors, protein kinases, transmembrane receptors, extracellular ligands and some external factors like oncogenic mutations, ubiquitin-proteasome pathway with epigenetic changes. Traditional anticancer drugs either alter DNA synthesis or control cell division while new drugs retard tumor growth or induce apoptosis. The deterioration of dopaminergic neurons in substantia nigra results in Parkinson’s disease with mental confusion, cognitive dysfunction and sleep disorder. Rheumatoid arthritis is characterized by inflammation, autoimmunity, joint destruction, deformity and premature mortality and treated mainly by anti-inflammatory and antirheumatic drugs. This review provides a comprehensive summary of objects which may act as potential targets for many health disorders.

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Sphingosine-1-Phosphate and Rheumatoid Arthritis: Pathological Implications and Potential Therapeutic Targets

Cited by 3 publications

References 130 publications

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

The sphingosine-1-phosphate receptor: A novel therapeutic target for multiple sclerosis and other autoimmune diseases

Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease

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