IF 15 1区医学

Neuron Pub Date : 2025-09-03 DOI: 10.1016/j.neuron.2025.08.006

Eran A Mukamel, Hanqing Liu, M Margarita Behrens, Joseph R Ecker

引用次数: 0

Reconstructed cell-type-specific rhythms in human brain link Alzheimer's pathology, circadian stress, and ribosomal disruption. 人脑中重建的细胞类型特异性节律与阿尔茨海默病病理、昼夜节律压力和核糖体破坏有关。

IF 15 1区医学

Neuron Pub Date : 2025-09-03 Epub Date: 2025-08-06 DOI: 10.1016/j.neuron.2025.07.010

Henry C Hollis, Ashish Sharma, Patrick W Sheehan, Leonard B Maggi, Jason D Weber, Jan A Hammarlund, David A Bennett, Vilas Menon, Erik S Musiek, Ron C Anafi

{"title":"Reconstructed cell-type-specific rhythms in human brain link Alzheimer's pathology, circadian stress, and ribosomal disruption.","authors":"Henry C Hollis, Ashish Sharma, Patrick W Sheehan, Leonard B Maggi, Jason D Weber, Jan A Hammarlund, David A Bennett, Vilas Menon, Erik S Musiek, Ron C Anafi","doi":"10.1016/j.neuron.2025.07.010","DOIUrl":"10.1016/j.neuron.2025.07.010","url":null,"abstract":"Alzheimer's disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing (snRNA-seq) from post-mortem cortical samples, we informatically estimated the relative circadian phases of 409 persons with and without AD dementia, reconstructing circadian expression profiles across cell types. Although core clock rhythms were preserved in AD, many cell-type-specific circadian outputs were disrupted. Rhythms in ribosomal biogenesis and oxidative phosphorylation were dampened across cell types. Similar losses in ribosomal gene expression rhythms were observed in amyloid precursor protein/presenilin 1 (APP/PS1) mice, which showed further reductions in ribosomal protein expression and polysome-mediated translation after circadian desynchrony. Exploratory computational modeling reveals that altered translation may contribute to the increased circadian variability seen in AD patients. These findings reveal altered cell-type-specific circadian output rhythms in the brains of AD-affected patients and highlight disrupted ribosomal rhythms as a feature of AD.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2822-2838.e7"},"PeriodicalIF":15.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The neuroscience of brain cancers. 脑癌的神经科学。

IF 15 1区医学

Neuron Pub Date : 2025-09-03 DOI: 10.1016/j.neuron.2025.07.012

Michelle Monje

引用次数: 0

Next stop: Cancer neuroscience. 下一站：癌症神经科学。

IF 15 1区医学

Neuron Pub Date : 2025-09-03 DOI: 10.1016/j.neuron.2025.08.011

Benedicte Babayan, Ted Dobie

引用次数: 0

Novel approaches to clinical trial design in cancer neuroscience. 癌症神经科学临床试验设计的新方法。

IF 15 1区医学

Neuron Pub Date : 2025-09-03 DOI: 10.1016/j.neuron.2025.08.015

Gregory Jones, Jennifer L Anderson, Phuong T T Nguyen, Frederico O Gleber-Netto, William L Hwang, Vinay K Puduvalli, Michelle Monje, Moran Amit

{"title":"Novel approaches to clinical trial design in cancer neuroscience.","authors":"Gregory Jones, Jennifer L Anderson, Phuong T T Nguyen, Frederico O Gleber-Netto, William L Hwang, Vinay K Puduvalli, Michelle Monje, Moran Amit","doi":"10.1016/j.neuron.2025.08.015","DOIUrl":"10.1016/j.neuron.2025.08.015","url":null,"abstract":"The emerging field of cancer neuroscience has revealed profound bidirectional interactions between the nervous system and cancer cells, identifying novel therapeutic vulnerabilities across diverse malignancies. This review examines the unique challenges and strategies for translating these insights into effective therapies. We propose innovative approaches to overcome these barriers through drug repurposing, enhanced biomarker development, and optimized trial designs. Repurposing neuroactive drugs with established safety profiles offers an accelerated path to clinical impact, particularly for targeting glutamatergic, adrenergic, and neurotrophic signaling pathways. Emphasizing mitigation of neurotoxicity and improved patient quality of life will be paramount moving forward. Repurposed agents that show preliminary potential for \"dual use\" (i.e., simultaneous toxicity mitigation and synergistic anti-tumor effects) are highlighted for special consideration. Master protocols and window-of-opportunity trials provide platforms to rapidly validate mechanisms while addressing patient-centered outcomes. By systematically addressing these foundational elements across disciplines, cancer neuroscience can translate its profound mechanistic insights into meaningful therapeutic advances for patients with treatment-resistant malignancies.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 17","pages":"2791-2813"},"PeriodicalIF":15.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Wired to spread: Neural regulation of metastasis. 有线传播：转移的神经调节。

IF 15 1区医学

Neuron Pub Date : 2025-09-03 DOI: 10.1016/j.neuron.2025.07.009

Erica K Sloan, Aeson Chang

引用次数: 0

Of hope from fading will: Interoceptive signaling and the behavioral biology of cachexia. 希望从消退的意志：内感受信号和恶病质的行为生物学。

IF 15 1区医学

Neuron Pub Date : 2025-09-03 DOI: 10.1016/j.neuron.2025.06.019

Tobias Janowitz

引用次数: 0

Neural basis of transcutaneous electrical nerve stimulation for neuropathic pain relief. 经皮神经电刺激缓解神经性疼痛的神经基础。

IF 15 1区医学

Neuron Pub Date : 2025-09-01 DOI: 10.1016/j.neuron.2025.08.010

Shuai Liu, Sha-Sha Long, Fanfei Li, Huan Yang, Shaofeng Pu, Dongping Du, Xin Luo, Yu-Qiu Zhang, Qingjian Han

{"title":"Neural basis of transcutaneous electrical nerve stimulation for neuropathic pain relief.","authors":"Shuai Liu, Sha-Sha Long, Fanfei Li, Huan Yang, Shaofeng Pu, Dongping Du, Xin Luo, Yu-Qiu Zhang, Qingjian Han","doi":"10.1016/j.neuron.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.010","url":null,"abstract":"Existing treatments for chronic pain often prove ineffective and carry adverse side effects, highlighting the need for better analgesics, including non-pharmacological treatments. We demonstrate that transcutaneous electrical nerve stimulation (TENS), when repeatedly applied during the early phase of nerve injury in mice, produces sustained analgesic effects by activating the dorsal column nucleus (DCN)-thalamic-cortical pathway, which transmits vibration, discriminative touch, and proprioception. Mechanistically, TENS selectively activates glutamatergic neurons in the DCN (DCNGlu) via exciting Aβ low-threshold mechanoreceptors (Aβ-LTMRs) in dorsal root ganglia (DRGs). These DCNGlu neurons project to a distinct subset of glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLDCN, Glu), separate from neurons receiving spinal dorsal horn input (VPLSDH, Glu). VPLDCN, Glu neurons form monosynaptic connections with layer 5 neurons in the somatosensory hindlimb cortex (S1HL), mediating TENS-induced analgesia. Our findings disclosed a neural basis of TENS-mediated pain relief and offered a promising therapeutic target for neuropathic pain.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation. 多丝氨酸介导的FAF2/UBXD8靶向改善tau聚集。

IF 15 1区医学

Neuron Pub Date : 2025-08-29 DOI: 10.1016/j.neuron.2025.08.002

Meaghan Van Alstyne, Georgia Brown, Vanessa L Nguyen, Mani Ramaswami, Charles A Hoeffer, Roy Parker

{"title":"Polyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation.","authors":"Meaghan Van Alstyne, Georgia Brown, Vanessa L Nguyen, Mani Ramaswami, Charles A Hoeffer, Roy Parker","doi":"10.1016/j.neuron.2025.08.002","DOIUrl":"10.1016/j.neuron.2025.08.002","url":null,"abstract":"Tau aggregation is a hallmark of several neurodegenerative disorders, and the gain of toxic function of misfolded tau species is linked to pathobiology. Herein, we identified proteins that limit tau aggregation when targeted to tau aggregates by polyserine domains. Polyserine targeting was most effective at mitigating tau aggregation when fused to the vasolin-containing protein (VCP) adaptor protein fas-associated factor family member 2/UBX domain-containing protein 8 (FAF2/UBXD8). Surprisingly, FAF2/UBXD8 suppresses tau aggregation independent of VCP but does require ubiquitination, membrane localization, and a ubiquitin regulator X (UBX) domain. Validation in animal models demonstrated that polyserine-targeted FAF2/UBXD8 rescues tau-induced neurodegeneration in Drosophila. Further, delivery of targeted FAF2/UBXD8 reduced gliosis, seeding capacity, and insoluble tau levels in PS19 tau transgenic mice while improving contextual fear conditioning. Collectively, our findings highlight polyserine as a tau-targeting strategy and identify targeted FAF2/UBXD8 as a potent suppressor of tau pathology.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aberrant coupling of glutamate and tyrosine kinase receptors enables neuronal control of brain-tumor growth. 谷氨酸和酪氨酸激酶受体的异常偶联使神经元控制脑肿瘤的生长。

IF 15 1区医学

Neuron Pub Date : 2025-08-27 DOI: 10.1016/j.neuron.2025.08.005

Corina Anastasaki, Rui Mu, Chloe M Kernan, Xuanwei Li, Rasha Barakat, Joshua P Koleske, Yunqing Gao, Olivia M Cobb, Xinguo Lu, Charles G Eberhart, Joanna J Phillips, Jennifer M Strahle, Sonika Dahiya, Steven J Mennerick, Fausto J Rodriguez, David H Gutmann

{"title":"Aberrant coupling of glutamate and tyrosine kinase receptors enables neuronal control of brain-tumor growth.","authors":"Corina Anastasaki, Rui Mu, Chloe M Kernan, Xuanwei Li, Rasha Barakat, Joshua P Koleske, Yunqing Gao, Olivia M Cobb, Xinguo Lu, Charles G Eberhart, Joanna J Phillips, Jennifer M Strahle, Sonika Dahiya, Steven J Mennerick, Fausto J Rodriguez, David H Gutmann","doi":"10.1016/j.neuron.2025.08.005","DOIUrl":"10.1016/j.neuron.2025.08.005","url":null,"abstract":"Direct and paracrine neuron-cancer interactions govern tumor development and progression. While neuron-elaborated neurotransmitters, like glutamate, support neoplastic growth, the mechanism underlying tumor intracellular mitogenic signaling and proliferation remains an unresolved question in cancer neuroscience. Herein, we discover that glutamate receptor (GluR) stimulation phosphorylates sarcoma proto-oncogene (Src) to activate platelet-derived growth factor (PDGF) receptor-α (PDGFRα)-dependent extracellular-regulated kinase (ERK) signaling and drive glioma growth. Using single-cell transcriptomic datasets and unique laboratory-generated humanized models of the most common brain tumor in children (pilocytic astrocytoma [PA]), we identify glutamatergic pathway enrichment in tumor cells, where glutamate increases PA proliferation without changing membrane depolarization. Aberrant GRID2 and GRIK3 GluR expression increases rat sarcoma (RAS)/ERK signaling by selective Src-mediated PDGFRα activation. Moreover, genetic or pharmacologic GRID2/GRIK3 and PDGFRA inhibition reduce PDGFRα/RAS/ERK activation, PA cell proliferation, and PA xenograft growth. Taken together, these observations establish a conceptual framework for understanding similar neurotransmitter dependencies in other cancers.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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