Dataset Information

Leptin Functions in Infectious Diseases.

ABSTRACT: Leptin, a pleiotropic protein has long been recognized to play an important role in the regulation of energy homeostasis, metabolism, neuroendocrine function, and other physiological functions through its effects on the central nervous system (CNS) and peripheral tissues. Leptin is secreted by adipose tissue and encoded by the obese (ob) gene. Leptin acts as a central mediator which regulates immunity as well as nutrition. Importantly, leptin can modulate both innate and adaptive immune responses. Leptin deficiency/resistance is associated with dysregulation of cytokine production, increased susceptibility toward infectious diseases, autoimmune disorders, malnutrition and inflammatory responses. Malnutrition induces a state of immunodeficiency and an inclination to death from communicable diseases. Infectious diseases are the disease of poor who invariably suffer from malnutrition that could result from reduced serum leptin levels. Thus, leptin has been placed at the center of many interrelated functions in various pathogenic conditions, such as bacterial, viruses and parasitic infections. We review herein, the recent advances on the role of leptin in malnutrition in pathogenesis of infectious diseases with a particular emphasis on parasitic diseases such as Leishmaniasis, Trypanosomiasis, Amoebiasis, and Malaria.

SUBMITTER: Maurya R

PROVIDER: S-EPMC6275238 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Leptin Functions in Infectious Diseases.

Maurya Radheshyam R Bhattacharya Parna P Dey Ranadhir R Nakhasi Hira L HL

Frontiers in immunology 20181126

Leptin, a pleiotropic protein has long been recognized to play an important role in the regulation of energy homeostasis, metabolism, neuroendocrine function, and other physiological functions through its effects on the central nervous system (CNS) and peripheral tissues. Leptin is secreted by adipose tissue and encoded by the obese (<i>ob</i>) gene. Leptin acts as a central mediator which regulates immunity as well as nutrition. Importantly, leptin can modulate both innate and adaptive immune r ...[more]

PMID: 30534129

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Project description:The Immucillins are chemically stable analogues that mimic the ribocation and leaving-group features of N-ribosyltransferase transition states. Infectious disease agents often rely on ribosyltransferase chemistry in pathways involving precursor synthesis for nucleic acids, salvage of nucleic acid precursors, or synthetic pathways with nucleoside intermediates. Here, we review three infectious agents and the use of the Immucillins to taget enzymes essential to the parasites. First, DADMe-Immucillin-G is a purine nucleoside phosphorylase (PNP) inhibitor that blocks purine salvage and shows clinical potential for treatment for the malaria parasite Plasmodium falciparum, a purine auxotroph requiring hypoxanthine for purine nucleotide synthesis. Inhibition of the PNPs in the host and in parasite cells leads to apurinic starvation and death. Second, Helicobacter pylori, a causative agent of human ulcers, synthesizes menaquinone, an essential electron transfer agent, in a pathway requiring aminofutalosine nucleoside hydrolysis. Inhibitors of the H. pylori methylthioadenosine nucleosidase (MTAN) are powerful antibiotics for this organism. Synthesis of menaquinone by the aminofutalosine pathway does not occur in most bacteria populating the human gut microbiome. Thus, MTAN inhibitors provide high-specificity antibiotics for H. pylori and are not expected to disrupt the normal gut bacterial flora. Third, Immucillin-A was designed as a transition state analogue of the atypical PNP from Trichomonas vaginalis. In antiviral screens, Immucillin-A was shown to act as a prodrug. It is active against filoviruses and flaviviruses. In virus-infected cells, Immucillin-A is converted to the triphosphate, is incorporated into the viral transcript, and functions as an atypical chain-terminator for RNA-dependent RNA polymerases. Immucillin-A has entered clinical trials for use as an antiviral. We also summarize other Immucillins that have been characterized in successful clinical trials for T-cell lymphoma and gout. The human trials support the potential development of the Immucillins in infectious diseases.

Dataset Information

Leptin Functions in Infectious Diseases.

Publications

Leptin Functions in Infectious Diseases.

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