BioEssays最新文献

Neuron–glioma interactions are critical drivers of glioma progression, with neuronal activity promoting tumor growth and invasion through paracrine signaling and direct synaptic input. Beyond well-established glutamatergic synapses, recent discoveries revealed that GABAergic interactions also contribute to glioma proliferation. Here, we focus on how glioma cells decode neuronal cues via epigenetic mechanisms, including enhancer reprogramming, chromatin remodeling, and rewiring of 3D genome organization, with transcriptions factors such as SMAD3 and PITX1 orchestrating transcriptional programs that sustain neuron-to-glioma communication. Additionally, recent integration of multi-omics data highlights gene regulatory networks linked to GABAergic signaling as contributors to glioblastoma (GB) pathogenesis. We also underscore the distinct roles of GABAergic signaling across glioma subtypes, noting that, in GB, GABA-related metabolic and paracrine mechanisms, rather than synaptic input, may drive tumor progression. Understanding how epigenetic reprogramming facilitates glioma integration into neural circuits opens new avenues to disrupt these malignant neuron–glioma interactions by targeting the epigenetic machinery.

The reduction of adult neurogenesis in the human brain, compared to other vertebrate species, has been proposed to result from an active counter-selection to permit the stability of circuits needed for long-term memorization and higher cognitive abilities. Here, bringing forward behavior studies and evolution-based observations, we discuss the benefits of adult neurogenesis and data suggesting that its loss is unlinked with cognitive levels. Considering cell lineages and functional assays, we further note that human-specific genomic features (such as novel gene variants or regulatory sequences) frequently hit pathways that may lead to the premature exhaustion of embryonic neural progenitors after the developmental phase of cortex formation. We propose that reduced adult neurogenesis in humans may be a tradeoff for these changes, themselves selected for to permit the enlargement and complexification of the cerebral cortex during development.

The amyloid-β peptide (Aβ), implicated in Alzheimer's disease, exhibits significant polymorphism. At the monomer level, Aβ can adopt disordered, helical, and β-hairpin structures, influenced by environmental conditions. Both oligomeric and fibrillar states, characterized by the prevalence of β-sheets, are polymorphic in the arrangement of β-strands. This chameleon-like behavior arises from Aβ’s unique sequence and relatively flat energy landscape, which facilitates aggregation and may contribute to the prevalence of Alzheimer's disease, while also enabling disaggregation, thus slowing disease progression. In contrast, Creutzfeldt-Jakob disease, which is much rarer, progresses far more rapidly, likely due to the steeper energy landscape of the prion protein.

Mitochondrial membrane potential is highly dependent on coupled as well as uncoupled respiration. While brown adipose tissue (BAT) mediates non-shivering thermogenesis (NST), a highly adaptive bioenergetic process critical for energy metabolism, the relationship of coupled and uncoupled respiration in thermogenic adipocytes remains complicated. Uncoupling protein 1 (UCP1)-mediated proton leak is the primary driver of NST, but recent studies have shown that oxidative phosphorylation may be an underappreciated contributor to UCP1-dependent NST. Here, we highlight the role of ATP synthase for BAT thermogenesis and discuss the implications of fine-tuning adrenergic signaling in brown adipocytes by the protein inhibitory factor 1 (IF1). We conclude by hypothesizing future directions for mitochondrial research, such as investigating the potential role of IF1 for mitochondrial substrate preference, structural dynamics, as well as its role in cell fate decision and differentiation.

Sphingolipids are a structurally unique, widespread, and diverse family of lipids. Serine palmitoyltransferase (SPT) is the first and rate-limiting enzyme required for the synthesis of all sphingolipids. Not unexpectedly, SPT is highly regulated. SPT is a multi-subunit enzyme, the level of activity of which is controlled by the regulatory subunits known as the ORMDLs. Here, we discuss how the regulation of SPT activity is accomplished by multiple mechanisms, underscoring the importance of this regulation. A rapid homeostatic regulation of SPT, monitoring cellular sphingolipid levels, is mediated by the direct binding of the central sphingolipid ceramide to the SPT/ORMDL complex. This acute regulation is overlaid by a longer-term regulation in which ORMDL is removed from the remainder of the SPT complex and trafficked for degradation, resulting in enhanced SPT activity. A third level of regulation is conferred by the inclusion of specific isoforms of the subunits of SPT into the complex. The isoform composition of the SPT complex dictates both the sensitivity of the complex to levels of cellular sphingolipid and the molecular species of sphingoid backbone that are produced. Here we discuss the mechanisms, interplay, and physiological roles of these three levels of regulation of sphingolipid biosynthesis.