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Crosstalk between degradation and bioenergetics: how autophagy and endolysosomal processes regulate energy production

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Neural Regeneration Research 2025年第3期20卷 671-681页

作者： Angelid Pabon Jagannatham Naidu Bhupana Ching-On Wong department of biological sciences Rutgers UniversityNewarkNJUSA

Cells undergo metabolic reprogramming to adapt to changes in nutrient availability, cellular activity, and transitions in cell states. The balance between glycolysis and mitochondrial respiration is crucial for energy production, and metabolic reprogramming stipulates a shift in such balance to optimize both bioenergetic efficiency and anabolic requirements. Failure in switching bioenergetic dependence can lead to maladaptation and pathogenesis. While cellular degradation is known to recycle precursor molecules for anabolism, its potential role in regulating energy production remains less explored. The bioenergetic switch between glycolysis and mitochondrial respiration involves transcription factors and organelle homeostasis, which are both regulated by the cellular degradation pathways. A growing body of studies has demonstrated that both stem cells and differentiated cells exhibit bioenergetic switch upon perturbations of autophagic activity or endolysosomal processes. Here, we highlighted the current understanding of the interplay between degradation processes, specifically autophagy and endolysosomes, transcription factors, endolysosomal signaling, and mitochondrial homeostasis in shaping cellular bioenergetics. This review aims to summarize the relationship between degradation processes and bioenergetics, providing a foundation for future research to unveil deeper mechanistic insights into bioenergetic regulation.

关键词： autophagy bioenergetics endolysosome energy production glycolysis metabolic reprogramming mitochondria

Astrocytes integrate time and space

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Neural Regeneration Research 2025年第2期20卷 467-468页

作者： Justin Lines department of biological sciences Columbia UniversityNew YorkNYUSA

Astrocytes read and react to synaptic transmission through tripartite synapses,where the binding of neurotransmitters onto astrocytic receptors triggers an increase in intracellular *** investigations have revealed that astrocytes exhibit two distinct states of intracellular calcium activity:(1)graded subcellular localized clusters with independently active microdomains,likely influenced by nearby synaptic events,and(2)whole-cell astrocyte calcium surges,believed to result from the coordinated activation of multiple ***,astrocyte calcium responses are not solely graded;instead,a spatial threshold of intracellular calcium activity can be overcome to elicit an astrocyte calcium *** these calcium responses,in turn,initiate downstream signaling pathways capable of modifying synaptic communication and overall network *** summary,astrocytes can function as integrators of local synaptic events,actively contributing to information processing within the brain.

关键词： graded integrate instead

Alpha-synuclein in mitochondrial dysfunction:opportunities or obstacles

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Neural Regeneration Research 2025年第1期20卷 197-198页

作者： Shermali Gunawardena department of biological sciences The State University of New York at BuffaloBuffaloNYUSA

Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still *** notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is *** date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.

关键词： dysfunction homeostasis Alpha

Apolipoprotein E elicits targetdirected miRNA degradation to maintain neuronal integrity

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Neural Regeneration Research 2025年第9期20卷 2577-2578页

作者： Jiazi Tan Chin-Tong Ong Temasek Life sciences Laboratory National University of SingaporeSingapore department of biological sciences National University of SingaporeSingapore

Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous *** are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.

关键词： metabolism glycoprotein maintain

Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

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Neural Regeneration Research 2025年第4期20卷 1015-1030页

作者： Ruoyu Huang Qiuyu Pang Lexin Zheng Jiaxi Lin Hanxi Li Lingbo Wan Tao Wang department of Forensic Science School of Basic Medicine and Biological SciencesSuzhou Medicine College of Soochow UniversitySuzhouJiangsu ProvinceChina

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and *** plays a key role in the establishment and maintenance of the central nervous *** brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and *** brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental ***,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system *** hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and *** cholesterol levels are associated with the risk of intracerebral ***,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell *** cholesterol accumulation in the brain has been found after intracerebral *** this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell *** also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

关键词： cell death cholesterol metabolism intracerebral hemorrhage myelination therapeutic target

Engendered nanoparticles for treatment of brain tumors

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Oncology Research 2025年第1期33卷 15-26页

作者： SOROUSH SOLEYMANI MOHAMMAD DOROUDIAN MAHDIEH SOEZI ALI BELADI KIARASH ASGARI ASO MOBARAKSHAHI ARYANA AGHAEIPOUR RONAN MACLOUGHLIN department of Cell and Molecular Biology School of Biological SciencesUniversity of LeicesterLeicesterLE17RHUK department of Cell and Molecular Biology Faculty of Biological SciencesKharazmi UniversityTehran15719-14911Iran Cancer Epidemiology Research Center Aja University of Medical SciencesTehran14117-18541Iran Medical Biotechnology Research Center Aja University of Medical SciencesTehran14117-18541Iran department of Life sciences Faculty of Natural SciencesImperial College LondonLondonSW72AZUK School of Pharmacy and Biomolecular sciences Royal College of Surgeons in Ireland(RCSI)DublinD02 YN77Ireland Research and Development Science and Emerging TechnologiesAerogen Ltd.Galway Business ParkGalwayH91 HE94Ireland School of Pharmacy and Pharmaceutical sciences Trinity CollegeDublinD02 PN40Ireland

Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain *** median survival time is typically less than a year after *** of the major challenges in treating these cancers is the efficiency of the transport of drugs to the central nervous *** blood-brain barrier is cooperating with advanced stages of *** blood-brain barrier poses a significant challenge to delivering systemic medications to brain *** delivery systems have emerged as promising tools for effectively crossing this ***,the development of smart nanoparticles brings new hope for cancer diagnosis and *** nanoparticles improve drug delivery efficiency,allowing for the creation of targeted and stimuli-responsive delivery *** review highlights recent advancements in nanoparticle and smart nanoparticle technologies for brain cancer treatment,exploring the range of nanoparticles under development,their applications,targeting strategies,and the latest progress in enhancing transport across the blood-brain *** also addresses the ongoing challenges and potential benefits of these innovative approaches.

关键词： Nanoparticles Smart nanoparticles Stimuli responsive nanoparticles Targeted nanoparticles Blood-brain barrier(BBB) Brain cancer

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

Crustal magma oxidation state and endowments in porphyry copper deposits

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Science China Earth sciences 2025年第1期68卷 226-236页

作者： Yumin AI Massimo CHIARADIA Chao WU Huayong CHEN Key Laboratory of Mineralogy and Metallogeny Guangzhou Institute of Geochemistry Chinese Academy of Sciences University of Chinese Academy of sciences department of Earth sciences University of Geneva Guangdong Provincial Key Laboratory of Mineral Physics and Materials

Porphyry copper deposits（PCDs） supply the majority of the world's copper（Cu） as well as significant amounts of molybdenum（Mo） and gold（Au）. The formation of these deposits is controlled by a variety of geological factors, among which the magmatic oxidation is one of the focuses of current research. This study investigates the redox characteristics of arc magmas by analyzing the ratio of vanadium（V） to scandium（Sc） and its correlation with the oxygen fugacity （fO2） of magmas from arcs of various crustal thicknesses globally. We compiled an extensive dataset of published V/Sc values and studied the partition coefficients of Vand Sc between minerals and silicate melts across various magmatic environments. The results demonstrate that fractional crystallization of magnetite markedly reduces V/Sc values of the residual melt. Furthermore, magnesium number（Mg#） at the onset of magnetite fractionation is strongly positively correlated with fO2of the equilibrium magma. Based on this,the oxidation of arc magmas from different crustal thicknesses can be evaluated. The result suggests that magmas generated in crusts thicker than 20 km tend to be more oxidized with increasing crust thickness. This trend is attributed to enhanced intracrustal differentiation processes involving garnet and amphibole, particularly in mature island and continental arcs. In contrast,magmas in thinner arc crusts（<20 km）, which are significantly influenced by subducted slab materials, display higher oxidation states than most of their thicker crust counterparts. These findings suggest that both subduction dynamics and crustal thickness play a vital role in determining the oxidation state of arc magmas and, consequently, their capacity to generate PCDs. Highly oxidized, primitive arc magmas are less favorable for PCD formation due to that they tend to experience magnetite fractionation and thus sulfide saturation in the early stage of magma evolution, a process leading to copper depletion. On the contra

关键词： Magma evolution V/Sc systematics Magnetite Oxygen fugacity Porphyry copper deposits

Spatiotemporal evolution of Ediacaran-Cambrian(ca. 551–523 Ma)sponges in South China and their simulated contributions to marine oxygenation

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Science China Earth sciences 2025年

作者： Yan YE Lei ZHANG Can CHEN Shan CHANG Yuhao YI Qinglai FENG State Key Laboratory of geological Processes and Mineral Resources China University of Geosciences(Wuhan) School of Earth Science China University of Geosciences(Wuhan) department of Geology Lund University Institute of Sedimentary Geology Chengdu University of Technology Key Laboratory of Deep-time Geography and Environment Reconstruction and Applications of Ministry of Natural Resources Chengdu University of Technology Second geological Brigade of Hubei geological Bureau College of Urban and Environmental sciences Hubei Normal University Exploration and Development Research Institute SINOPEC Jianghan Oilfield Company

The origin and evolution of sponges have attracted interest, not only because they are among the most basal metazoans, but also because they act as important ecological engineers in the ocean. Previous research suggested that sponge groups diversified quickly during the Cambrian Series 2, while Terreneuvian sponge fossils are conspicuously rare and poorly substantiated. Yet, an increasing number of sponge spicules have been reported from the Ediacaran-Cambrian(E-C, ca.551–523 Ma) transitional carbonates/cherts worldwide, particularly in South China, which calls for updated discussions. Ocean oxygenation has been widely proposed to play a critical role in organismal evolution, but its relationship with sponges is unclear and falls into a “chicken-egg” dilemma. In this study, we summarize reported sponge spicule distributions from five E-C sections in South China to investigate the early evolutionary pattern of siliceous sponges. According to current stratigraphic correlation,monaxons first appear in the late Ediacaran in the intrashelf basin-slope area, and then potentially expand to the continental shelf and deep basin in the lower Cambrian. In these sections, the abundance, size, and diversity of monaxons increase upwards,followed by the appearance of diaxons, triaxons and then polyactines. Despite the uncertain affinity of the sponge fossils, it is possible that siliceous hexactinellids evolved later than siliceous demosponges, given that the earliest spicule assemblages are exclusively composed of monaxons, which commonly form bundles comparable to modern demosponges. New geochemical data from the Sifangjing section, Guizhou Province and the Yanziqiao section, Hunan Province, South China show that the appearance of sponges usually corresponds to anoxic environment. In addition, we applied the recently proposed biological Pump, Oxygen and Phosphorus(BPOP) model to trace the evolution of oceanic oxygen concentrations with the radiation of sponges. The results indic

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