Current Opinion in Chemical Biology最新文献

Endogenously formed reactive molecules, such as lipid peroxides, 4-hydroxynonenal, methylglyoxal and other reactive oxygen species, can have major effects on cells. Accumulation of these molecules is counteracted by antioxidant enzymes, including the glutathione (GSH) and thioredoxin (Trx) systems, in turn regulated by the KEAP1/NRF2 system. Receptor tyrosine kinases (RTK) and their counteracting protein tyrosine phosphatases (PTP) are also modulated through redox regulation of PTP activities. The cytosolic selenoprotein thioredoxin reductase (TXNRD1) is particularly prone to attack at its easily accessible catalytic selenocysteine (Sec) residue by reactive electrophilic compounds. Therefore, we here discuss how endogenously formed electrophiles can modulate RTK/PTP signaling in a concentration- and time dependent manner by reactions either directly or indirectly linking TXNRD1 with the KEAP1/NRF2 system. Moreover, recent findings suggest that endogenous formation of peroxymonocarbonate can efficiently inhibit PTP activities and stimulate RTK signaling, seemingly bypassing PTP reduction as otherwise supported by the GSH/Trx systems.

Localized protein translation occurs through trafficking of mRNAs and protein translation machineries to different compartments of the cell, leading to rapid on-site synthesis of proteins in response to signaling cues. The spatiotemporally precise nature of the local translation process necessitates continual developments of technologies reviewed herein to visualize and map biomolecular components and the translation process with better spatial and temporal resolution and with fewer artifacts. We also discuss approaches to control local translation, which can serve as a design paradigm for subcellular genetic devices for eukaryotic synthetic biology.

Lectin–glycan interactions play a crucial role in the immune system. An important class of lectins in the innate immune system is myeloid C-type lectin receptors (CLRs). Myeloid CLRs act as pattern recognition receptors and are predominantly expressed by myeloid cells, such as macrophages, dendritic cells, and neutrophils. In innate immunity, CLRs contribute to self/non-self discrimination. While the recognition of pathogen-associated molecular patterns (PAMPs) by CLRs may contribute to a protective immune response, CLR engagement can also be exploited by pathogens for immune evasion. Since various CLRs act as endocytic receptors and trigger distinct signaling pathways in myeloid cells, CLR targeting has proven useful for drug/antigen delivery into antigen-presenting cells and the modulation of immune responses. This review covers recent discoveries of pathogen/CLR interactions and novel approaches for CLR targeting within the period of the past two years.

The ancient messenger molecule hydrogen sulfide (H₂S) modulates myriad signaling cascades and has been conserved across evolutionary boundaries. Although traditionally known as an environmental toxin, H₂S is also synthesized endogenously to exert modulatory and homeostatic effects in a broad array of physiologic functions. Notably, H₂S levels are tightly physiologically regulated, as both its excess and paucity can be toxic. Accumulating evidence has revealed pivotal roles for H₂S in neuroprotection and normal cognitive function, and H₂S homeostasis is dysregulated in neurodegenerative conditions. Here, we review the normal neuroprotective roles of H₂S that go awry in Alzheimer's disease, the most common form of neurodegenerative disease.