Journal of Neurochemistry最新文献

{"title":"Altered Mitochondrial Bioenergetics and Calcium Kinetics in Young-Onset PLA2G6 Parkinson's Disease iPSCs","authors":"Thasneem Musthafa,&nbsp;Syed Kavish Nizami,&nbsp;Ankita Mishra,&nbsp;Gaiti Hasan,&nbsp;Renjitha Gopurappilly","doi":"10.1111/jnc.70059","DOIUrl":"https://doi.org/10.1111/jnc.70059","url":null,"abstract":"<p>Parkinson's disease (PD) has emerged as a multisystem disorder affecting multiple cellular and organellar systems in addition to the dopaminergic neurons. Disease-specific induced pluripotent stem cells (iPSCs) model early developmental changes and cellular perturbations that are otherwise inaccessible from clinical settings. Here, we report the early changes in patient-derived iPSCs carrying a homozygous recessive mutation, R741Q, in the <i>PLA2G6</i> gene. A gene-edited R747W iPSC line mirrored these phenotypes, thus validating our initial findings. Bioenergetic dysfunction and hyperpolarization of mitochondrial membrane potentials were hallmarks of the PD iPSCs. Further, a concomitant increase in glycolytic activity indicated a possible compensation for mitochondrial respiration. Elevated basal reactive oxygen species (ROS) and decreased catalase expression were also observed in the disease iPSCs. No change in autophagy was detected. These inceptive changes could be potential targets for early intervention of prodromal PD in the absence of disease-modifying therapies. However, additional investigations are crucial to delineate the cause-effect relationships of these observations.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase Separation and Prion-Like Aggregation of p53 Family Tumor Suppressors: From Protein Evolution to Cancer Treatment","authors":"Jerson L. Silva,&nbsp;Guilherme C. de Andrade,&nbsp;Elaine C. Petronilho,&nbsp;Gileno dos S. de Sousa,&nbsp;Michelle F. Mota,&nbsp;Julia Quarti,&nbsp;Francisca H. Guedes-da-Silva,&nbsp;Giulia D. S. Ferretti,&nbsp;Luciana P. Rangel,&nbsp;Tuane C. R. G. Vieira,&nbsp;Mayra A. Marques,&nbsp;Guilherme A. P. de Oliveira","doi":"10.1111/jnc.70055","DOIUrl":"https://doi.org/10.1111/jnc.70055","url":null,"abstract":"<p>Biomolecular condensates, formed through phase separation (PS), are essential in various physiological processes, but they can also transition into amyloid-like structures, contributing to diseases like cancer and neurodegenerative disorders. This review centers on the tumor suppressor protein p53 and its paralogs, p63 and p73, which play significant roles in cancer biology. Mutations in the <i>TP53</i> gene, present in over half of all malignant tumors, disrupt the function of p53 and contribute to cancer progression. Mutant p53 not only misfolds but also forms biomolecular condensates and amyloid-like aggregates, like the toxic amyloids seen in neurodegenerative diseases. These amyloid-like structures, characteristic of mutant p53, might be associated with its gain of function (GoF) in cancer. Recent in vitro and <i>in cell</i> studies demonstrate that mutant p53 can exert a prion-like effect on its paralogs, p63 and p73, which typically do not form amyloids under physiological conditions. Heparin inhibits the prion-like effect of mutant p53 on p63 and p73. These findings underscore the critical role of mutant p53 in promoting the aggregation of p63 and p73, and likely of other transcription factors, suggesting new therapeutic targets. The amyloid-like aggregation of mutant p53 is an excellent candidate target for cancer, as evidenced by recent studies. By understanding the phase transitions and amyloid formation of mutant p53, innovative diagnostic and treatment strategies have been explored to reveal and disrupt these processes, offering hope for improved cancer therapies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Psychological Stress and Spontaneous Tumour Regression on the Hippocampal Proteome in a Mouse Model of Breast Cancer","authors":"Myrthe Mampay,&nbsp;Gheed Al-Hity,&nbsp;Sara O. Rolle,&nbsp;Walla Alzboon,&nbsp;Nicolas A. Stewart,&nbsp;Melanie S. Flint,&nbsp;Graham K. Sheridan","doi":"10.1111/jnc.70052","DOIUrl":"https://doi.org/10.1111/jnc.70052","url":null,"abstract":"<p>Cognitive impairment is common in people diagnosed with breast cancer, but the molecular mechanisms that underlie maladaptive changes in the brain are unknown. The psychological stress of a cancer diagnosis is certainly a contributing factor. Here, we investigated alterations in the hippocampal proteome in response to both cancer and psychological stress using label-free quantitative mass spectrometry techniques. An orthotopic syngeneic model of triple-negative breast cancer (TNBC) was established by injecting Py230 cells into the mammary fat pads of female C57Bl/6 mice. Half of the mice were subjected to a daily restraint stress paradigm. Mice that experienced both cancer and restraint stress lost weight and displayed larger tumours compared to non-stressed mice. Their urinary corticosterone levels were also elevated, as measured by enzyme-linked immunosorbent assay. Non-stressed tumour-bearing mice displayed higher levels of TNFα in the prefrontal cortex (PFC) compared to stressed mice with cancer. Flow cytometry results suggested that the CD4⁺/CD8⁺ T cell ratios were also raised in non-stressed tumour-bearing mice compared to both controls and stressed mice with TNBC. Bioinformatic analysis of hippocampal proteomes indicated that cancer alone causes reduced mitochondrial respiration and ATP synthesis, as well as impaired glutamate recycling and synaptic plasticity. Moreover, daily stress in TNBC mice caused further mitochondrial dysfunction, increased oxidative phosphorylation, and altered lipid metabolism. Importantly, over half of the mammary tumours that initially developed spontaneously regressed after 7–9 weeks in these young immunocompetent mice. Tumour regression inhibited TNFα increases in the PFC. However, the hippocampal proteomes of tumour-bearing mice were largely similar to mice in which tumours regressed, suggesting that spontaneous regression of breast cancer confers lasting physiological dysregulations that impact hippocampal protein expression. This study in mice may help to identify molecular mechanisms responsible for long-term memory impairments in cancer survivors and reveal novel drug targets for cancer-related cognitive impairment.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IP3R2 Knockout Mice in Behavior: A Blessing or a Curse?","authors":"Joana Gonçalves-Ribeiro,&nbsp;Sandra H. Vaz","doi":"10.1111/jnc.70062","DOIUrl":"https://doi.org/10.1111/jnc.70062","url":null,"abstract":"<p>The inositol 1,4,5-triphosphate receptor type 2 (IP3R2) plays a critical role in intracellular calcium (Ca²⁺) signaling, particularly in astrocytes, where it mediates Ca²⁺ release from the endoplasmic reticulum. This mechanism is vital for astrocytic modulation of neuronal networks, impacting synaptic transmission and broader neural circuit functions. The IP3R2 knockout (IP3R2KO) mouse model has been instrumental in unraveling the nuances of astrocytic somatic Ca²⁺ dynamics and their implications for brain function. Despite early findings suggesting no significant behavioral or synaptic transmission changes in IP3R2KO mice, further research highlights the model's benefit in exploring cognitive, emotional, and neurodevelopmental processes. IP3R2KO mice revealed key insights into astrocytic Ca²⁺ signaling diversity, encompassing bulk somatic events and localized microdomain responses, which exhibit temporal and spatial variability. These animals retain alternative Ca²⁺ mechanisms, likely explaining the absence of severe phenotypes in some contexts. Nevertheless, IP3R2KO mice exhibit impairments in long-term memory retention, working memory, and fear memory, alongside age-related preservation of spatial memory, linking astrocytic IP3R2 signaling to higher-order cognitive functions. Additionally, studies suggest a connection between IP3R2 pathways and depression-like behaviors, with alterations in Brain-Derived Neurotrophic Factor (BDNF) levels and GABAergic signaling, highlighting its relevance to psychiatric conditions. Despite its limitations, such as residual astrocytic Ca²⁺ activity and inconsistent findings, the IP3R2KO model remains a valuable tool for studying astrocytic contributions to synaptic plasticity and brain function. This underscores the importance of integrating, rather than dismissing, the IP3R2KO model in the development of new methodologies for studying astrocytic Ca²⁺ dynamics. The use of this model will continue to elucidate the complex interplay between astrocytes and neuronal circuits, fostering advances in understanding astrocytic Ca²⁺ signaling's role in health and disease.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-Synuclein Demonstrates Varying Binding Affinities With Different Tau Isoforms","authors":"Anna-Lisa Fischer,&nbsp;Matthias Schmitz,&nbsp;Tobias Thom,&nbsp;Saima Zafar,&nbsp;Neelam Younas,&nbsp;Susana da Silva Correia,&nbsp;Angela da Silva Correia,&nbsp;Sezgi Canaslan Eyyuboglu,&nbsp;Inga Zerr","doi":"10.1111/jnc.70053","DOIUrl":"https://doi.org/10.1111/jnc.70053","url":null,"abstract":"<div>\u0000 \u0000 <p>The hallmark of various neurodegenerative diseases is the accumulation and aggregation of amyloidogenic proteins, such as amyloid-beta (Aβ) and tau in Alzheimer's disease (<span>AD</span>) and alpha-synuclein (aSyn) in synucleinopathies. Many neurodegenerative diseases express mixed pathology. For instance, Lewy bodies are reported in tauopathies and neurofibrillary tau-tangles are detected in synucleinopathies, suggesting a potential co-existence or crosstalk of misfolded aSyn and tau. In the present study, we investigated the binding characteristics of monomeric aSyn with different tau isoforms by using surface plasmon resonance (SPR) spectroscopy allowing monitoring direct protein–protein interactions and their potential co-localization using SH-SY5Y cells. The calculation of the binding parameters (association and dissociation rate constants) indicated the strongest binding affinity between aSyn and tau isoform 1N3R followed by tau 2N3R and tau 2N4R. Co-localization studies in SH-SY5Y cells, treated with aSyn and all six tau isoforms revealed an intracellular co-localization of aSyn with different isoforms of tau. Subcellular fractionation confirmed the cellular uptake and colocalization of tau and aSyn in the same compartment, showing their expression in membrane, nuclear, and cytoskeletal fractions. Understanding the intricate interplay between aSyn and tau is crucial for unraveling the pathophysiology of PD, <span>AD</span>, and related neurodegenerative disorders, ultimately paving the way for the development of effective treatments targeting this interaction. In conclusion, our data indicate that aSyn and tau are direct interaction partners with varying binding affinities depending on the tau isoform. This interaction may be significant for understanding the pathophysiology of dementia with mixed pathologies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demethylase FTO Regulates P2X3R Expression Contributing to the Mechanism of Hyperalgesia in Lumbar Disc Herniation","authors":"Jianpeng Chen,&nbsp;Yuanbin Wang,&nbsp;Yujian Peng,&nbsp;Kang Jia,&nbsp;Zelin Fan,&nbsp;Fengxian Jiang,&nbsp;Jun Yan,&nbsp;Qianliang Wang","doi":"10.1111/jnc.70058","DOIUrl":"https://doi.org/10.1111/jnc.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Lumbar disc herniation (LDH) is a common chronic orthopedic condition characterized by the protrusion of nucleus pulposus tissue, leading to low back and leg pain. Its pathophysiology remains poorly understood. The aim of this study was to investigate whether the demethylase Fat mass and obesity-associated protein (FTO) mediates the local translation of P2X3 receptors (P2X3R) in a rat model of LDH. The effect of this process on the excitability of dorsal root ganglion (DRG) cells was also examined, which may elucidate the peripheral molecular mechanisms underlying the specific pain sensitivity of LDH. LDH models were established in male Sprague–Dawley rats. Behavioral tests assessed mechanical and thermal pain thresholds and motor function. The expression of P2X3R and FTO in DRG was investigated by RT-qPCR, Western blot, and immunofluorescence. FTO and P2X3R were knocked down, and P2X3R methylation was examined by MeRIP to validate their roles. IL-1β and IL-6 levels were quantified by ELISA. Protein interactions were predicted using AutoDock, and DRG neuronal excitability was assessed using patch clamp recordings. Compared with the Sham group, the LDH group showed a reduction in the mechanical pain threshold of the hind limbs. There were no significant differences in motor function. IL-1β and IL-6 levels were increased in the LDH group. P2X3R and FTO expression increased in DRG, localized mainly to the cell membrane and colocalized with NeuN. Intrathecal injection of P2X3R-siRNA and FTO-siRNA was effective in increasing pain thresholds, reducing the expression of P2X3R and FTO, decreasing the excitability of neurons, and decreasing the levels of IL-1β and IL-6. RNA Methylation Immunoprecipitation (MeRIP) analysis revealed reduced m6A modification of P2X3R mRNA in the LDH group. AutoDock predicted hydrogen bond interactions between FTO and P2X3R. These findings suggest that FTO regulates local translation of P2X3R in DRG. This influences neuronal excitability and contributes to LDH-induced hyperalgesia.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Upregulation of FMRP Is Involved in Neuropathic Pain by Regulating GluN2B Activation in Rat Spinal Cord’","authors":"","doi":"10.1111/jnc.70057","DOIUrl":"https://doi.org/10.1111/jnc.70057","url":null,"abstract":"<p>\u0000 <span>Chen, L.</span>, <span>Guo, X.</span>, <span>Zhang, L.</span>, <span>Li, Y.</span>, <span>Zhou, L.</span>, <span>Zhao, J.</span>, <span>Luo, Y.</span>, <span>Hu, Y.</span>, <span>Chen, X.</span>, <span>Kang, X.</span>, <span>Fang, X.</span> and <span>Feng, Z.</span> (<span>2025</span>), <span>Upregulation of FMRP Is Involved in Neuropathic Pain by Regulating GluN2B Activation in Rat Spinal Cord</span>. <i>J Neurochem</i>, <span>169</span>: e70022. https://doi.org/10.1111/jnc.70022\u0000 </p><p>In the paper by Chen et al. (2025), the authorship footnotes were omitted.</p><p>Lei Chen and Xuejiao Guo contributed equally to this work and share first authorship.</p><p>Xiangming Fang and Zhiying Feng contributed equally to this work and share corresponding authorship.</p><p>We apologize for this error.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoaminergic Alterations at the Subregional Cervical and Thoracic Spinal Cord Level of Patients Within the FTD-ALS Continuum and Early-Onset AD: Low Thoracic Dopaminergic Activity in ALS","authors":"Annelies Heylen,&nbsp;Yannick Vermeiren,&nbsp;Peter Paul De Deyn,&nbsp;Debby Van Dam","doi":"10.1111/jnc.70046","DOIUrl":"https://doi.org/10.1111/jnc.70046","url":null,"abstract":"<div>\u0000 \u0000 <p>Early-onset neurodegeneration leads to cognitive and behavioral symptoms in frontotemporal dementia (FTD) and motor disturbances in amyotrophic lateral sclerosis (ALS). Despite distinct clinical profiles, more than half of FTD patients experience ALS-related symptoms and vice versa. Spinal cord monoamine neurotransmitter alterations were reported in ALS, but not yet in FTD. Therefore, we compared monoaminergic turnover across the FTD–ALS continuum. Reversed-phase, ultra-high-performance liquid chromatography with electrochemical detection was used to measure levels of the monoamines (nor)adrenaline ((N)A), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and their metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in five cervical and thoracic spinal cord regions in 10 FTD, 14 ALS, 6 mixed FTD–ALS, 14 early-onset Alzheimer's disease (EOAD), and 7 control (CONTR) individuals. At the cervical level, NA levels were lower in FTD-ALS versus CONTR, whereas the HVA/5-HIAA ratio was higher in ALS versus EOAD in the lateral funiculus. In the dorsal horn–intermediate gray matter, DA levels were decreased in FTD-ALS compared to FTD. At the thoracic level, DOPAC was lower in ALS than in FTD-ALS patients in the ventral and lateral funiculus, ventral horn, and dorsal horn–intermediate gray matter, as was the DOPAC/DA ratio in the lateral funiculus and dorsal horn–intermediate gray matter. Contrarily, HVA/DA turnover was lower in FTD-ALS than in FTD in the dorsal and ventral funiculus. We observed lower NA levels in FTD-ALS than in FTD in the ventral funiculus, and lower MHPG/NA turnover in the dorsal horn–intermediate gray matter. A levels were lower in ALS versus FTD. This study indicates differences in monoaminergic turnover across the FTD-ALS continuum, at the cervical and thoracic levels, with primarily a decrease in dopaminergic activity in ALS. Characterizing disease-specific neurochemical profiles for FTD, ALS, or FTD-ALS could contribute to the identification of novel interesting pharmacological targets.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Prion Systems in Saccharomyces cerevisiae","authors":"Reed B. Wickner,&nbsp;Yuho Hayashi,&nbsp;Herman K. Edskes","doi":"10.1111/jnc.70045","DOIUrl":"https://doi.org/10.1111/jnc.70045","url":null,"abstract":"<p>[PSI+] is a prion (infectious protein) of Sup35p, a subunit of the translation termination factor, and [URE3] is a prion of Ure2p, a mediator of nitrogen catabolite repression. Here, we trace the history of these prions and describe the array of anti-prion systems in <i>S. cerevisiae</i>. These systems work together to block prion infection, prion generation, prion propagation, prion segregation, and the lethal (and near-lethal) effects of most variants of these prions. Each system lowers the appearance of prions 2- to 15-fold, but together, ribosome-associated chaperones, the Hsp104 disaggregase, and the Sup35p-binding Upf proteins lower the frequency of [PSI+] appearance by ~5000-fold. [PSI+] variants can be categorized by their sensitivity to the various anti-prion systems, with the majority of prion isolates sensitive to all three of the above-mentioned systems. Yeast prions have been used to screen for human anti-prion proteins, and five of the Bag protein family members each have such activity. We suggest that manipulation of human anti-prion systems may be useful in preventing or treating some of the many human amyloidoses currently found to be prions with the same amyloid architecture as the yeast prions.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking the Mould: How the First Structure of a Deer Prion Suggests the Framework for Interspecies Strain Diversity and Transmission Barriers","authors":"Szymon W. Manka","doi":"10.1111/jnc.70050","DOIUrl":"https://doi.org/10.1111/jnc.70050","url":null,"abstract":"<p>Our Insight into the Structural Diversity of Prions Has Been Limited by Studies Focused on Rodent-Adapted Sheep (Scrapie) Prion Strains, Until Now. In a Recent Paper (Alam et al. 2024), the Caughey Research Group Presents the First Prion Structure from a Naturally Occurring Chronic Wasting Disease (CWD), Offering a Fresh Perspective.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}