Current Issues in Molecular Biology

292 KiB

Open AccessReview

DNA Topoisomerases of Kinetoplastid Parasites: Brief Overview and Recent Perspectives

by Sourav Saha, Somenath Roy Chowdhury and Hemanta K. Majumder

Curr. Issues Mol. Biol. 2019, 31(1), 45-62; https://doi.org/10.21775/cimb.031.045 - 05 Jun 2019

Cited by 6 | Viewed by 501

Topoisomerases are a group of enzymes that resolve DNA topological problems and aid in different DNA transaction processes viz. replication, transcription, recombination, etc. inside cells. These proteins accomplish their feats by steps of DNA strand(s) scission, strand passage or rotation and subsequent rejoining activities. Topoisomerases of kinetoplastid parasites have been extensively studied because of their unusual features. The unique presence of heterodimeric Type IB topoisomerase and prokaryotic 'TopA homologue' Type IA topoisomerase in kinetoplastids still generates immense interest among scientists. Moreover, because of their structural dissimilarity with the host enzymes, topoisomerases of kinetoplastid parasites are attractive targets for chemotherapeutic interventions to kill these deadly parasites. In this review, we summarize historical perspectives and recent advances in kinetoplastid topoisomerase research and how these proteins are exploited for drug targeting. Full article

527 KiB

Open AccessReview

Circadian Rhythms and Energy Metabolism Reprogramming in Parkinson's Disease

by Alexandre Vallée, Yves Lecarpentier and Jean-Noël Vallée

Curr. Issues Mol. Biol. 2019, 31(1), 21-44; https://doi.org/10.21775/cimb.031.021 - 04 Jun 2019

Cited by 11 | Viewed by 682

Abstract

Entropy rate is increased by several metabolic and thermodynamic abnormalities in neurodegenerative diseases (NDs). Changes in Gibbs energy, heat production, ionic conductance or intracellular acidity are irreversible processes impelling modifications of the entropy rate. The present review focuses on the thermodynamic implications in the reprogramming of cellular energy metabolism enabling in Parkinson's disease (PD) through the contrasting interplay of the molecular signaling pathways WNT/ β-catenin and PPARγ. In PD, WNT/β-catenin pathway is downregulated while PPARγ is upregulated. Thermodynamic behaviors of metabolic enzymes are modified by dysregulation of the canonical WNT/β-catenin pathway. Downregulation of WNT/β-catenin pathway leads to hypometabolism, oxidative stress and cell death through inactivation of glycolytic enzymes such as Glut, PKM2, PDK1, MCT-1, LDH-A but also to activation of PDH. In addition, in NDs, PPARγ is dysregulated even though it contributes to the regulation of several key circadian genes. PD processes may be considered as dissipative structures that exchange energy or matter with their environment far-from the thermodynamic equilibrium. Far-from-equilibrium thermodynamics are notions driven by circadian rhythms, which directly contribute to regulation of the molecular pathways WNT/β-catenin and PPARγ involved in the reprogramming of cellular energy metabolism enabling in Parkinson's disease. Full article

433 KiB

Open AccessReview

Hypothesis of Opposite Interplay between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma in Primary Central Nervous System Lymphomas

by Alexandre Vallée, Yves Lecarpentier and Jean- Noël Vallée

Curr. Issues Mol. Biol. 2019, 31(1), 1-20; https://doi.org/10.21775/cimb.031.001 - 16 Jan 2019

Cited by 20 | Viewed by 629

Abstract

Primary central nervous system lymphomas (PCNSLs) are angiocentric neoplasia which present dense monoclonal lymphocyte proliferation, and occur in brain parenchyma in 90% of the cases. Activated B-cell like Diffuse Large B-cell Lymphoma (ABC-DLBCL) subtype represents more than 90% of PCNSLs and is the most aggressive subtype with a cure rate of only 40%. One of the characteristics of ABC-DLBCL subtype is neuroinflammation through the activation of NF-kappaB pathway. c-Myc alterations and protein expression have been shown in aggressive DLBCL. c-Myc is considered as a key prognostic and predictive biomarker for survival in DLBCL, its expression is associated with worst survival rates. Although mRNA of c-Myc is increased by low levels gains of c-Myc, several studies have shown that c-Myc protein expression is overexpressed without c-Myc abnormalities. These high levels of c-Myc protein in DLBCL without genetic abnormalities suggest that c-Myc protein expression may be also increased by other mechanisms or signaling pathways which regulate its expression. In PCNSLs, the canonical WNT/beta- catenin pathway is upregulated while PPAR gamma is downregulated. The opposite interplay between WNT/beta-catenin pathway and PPAR gamma is reviewed here. Activation of WNT/beta-catenin pathway leads to the transcription of genes involved in cell proliferation, mitochondrial metabolism, protein synthesis, and tumor growth, such as c-Myc. PPAR gamma agonists induce the inhibition of several signaling pathways such as NF-kappaB, STAT, PI3K/Akt and WNT/beta-catenin pathway. Activation of PPAR gamma agonists may have a major negative key role in the regulation of PCNSLs progression. Full article

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Curr. Issues Mol. Biol., Volume 31, Issue 1 (April 2019) – 3 articles

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