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Olfactory receptors in neural regeneration in the central nervous system

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Neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia Garrigós Toni Capó Joan Serrano-Marín Rafael Rivas-Santisteban Jaume Lillo molecular Neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical Research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain department of Biochemistry and physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 980-994页

作者： Motomichi Fujita Hideo Suzuki Fumio Fukai department of molecular patho-physiology Tokyo University of ScienceNoda 278-8510ChibaJapan department of Gastroenterology University of TsukubaTsukuba 305-8575IbarakiJapan

Tenascin-C(TNC)is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies,including colon *** TNC is considered a negative prognostic factor for cancer patients,the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly *** previously found that TNC has a cryptic functional site and that a TNC peptide containing this site,termed TNIIIA2,can potently and persistently activate *** contrast,the peptide FNIII14,which contains a cryptic bioactive site within the fibronectin molecule,can inactivate *** review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer,particularly the major involvement of its cryptic functional site *** propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.

关键词： Tenascin-C TNIIIA2 Beta1-integrin Integrin activation Colitis-associated colorectal cancer Colon cancer

Cerebral organoids exhibit mature neurons and astrocytes and recapitulate electrophysiological activity of the human brain

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Neural Regeneration Research 2019年第5期14卷 757-761页

作者： Abraam M.Yakoub department of molecular and Cellular physiology Stanford University

Multiple protocols have been devised to generate cerebral organoids that recapitulate features of the developing human brain, including the presence of a large, multi-layered, cortical-like neuronal zone. However, the central question is whether these organoids truly present mature, functional neurons and astrocytes, which may qualify the system for in-depth molecular neuroscience studies focused at neuronal and synaptic functions. Here, we demonstrate that cerebral organoids derived under optimal differentiation conditions exhibit mature, fully functional neurons and astrocytes, as validated by immunohistological, gene expression, and electrophysiological, analyses. Neurons in cerebral organoids showed gene expression profiles and electrophysiological properties similar to those reported for fetal human brain. These important findings indicate that cerebral organoids recapitulate the developing human brain and may enhance use of cerebral organoids in modeling human brain development or investigating neural deficits that underlie neurodevelopmental and neuropsychiatric conditions, such as autism or intellectual disorders.

关键词： cerebral organoids human brain stem cells neurons astrocytes neurodevelopmental disorders neuropsychiatric disorders autism

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of physiology and Pharmacology Karolinska InstitutetStockholmSweden department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

A remembrance of Professor TP FENG

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生理学报 2007年第6期59卷 713-715页

作者： Richard W.Tsien department of molecular and Cellular physiology Stanford University

It is both an honor and pleasure to be given this opportunity to remember Professor TP FENG and his many *** made many important scientific discoveries,labored mightily to establish firmly physiology and Neuroscience in China,and was a major force in setting a high standard for scientific *** is safe to say that the past and future of Neuroscience in China would be very different had Professor FENG not provided leadership,by dint of organization,persuasion and strong personal example.

关键词：神经系统科学中国冯德培生理学院士科研教学

Randomness in the Hybrid Modeling and Simulation of Insulin Secretion Pathways in Pancreatic Islets

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Tsinghua Science and Technology 2015年第5期20卷 441-452页

作者： Yang Pu David C.Samuels Layne T.Watson Yang Cao the department of Computer Science Virginia Polytechnic Institute and State University the department of molecular physiology and Biophysics Vanderbilt University

Insulin secreted by pancreatic islet ˇ-cells is the principal regulating hormone of glucose *** of insulin secretion may cause glucose to accumulate in the blood, and result in diabetes *** deterministic models of the insulin secretion pathway have been developed, the stochastic aspect of this biological pathway has not been explored. The first step in this direction presented here is a hybrid model of the insulin secretion pathway, in which the delayed rectifying KCchannels are treated as stochastic events. This hybrid model can not only reproduce the oscillation dynamics as the deterministic model does, but can also capture stochastic dynamics that the deterministic model does not. To measure the insulin oscillation system behavior, a probability-based measure is proposed and applied to test the effectiveness of a new remedy.

关键词： insulin secretion mathematical modeling hybrid model and simulation stochastic dynamics

Two Potent α3/5 Conotoxins from Piscivorous Conus achatinus

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Acta Biochimica et Biophysica Sinica 2007年第6期39卷 438-444页

作者： Geoffrey CHEW Edward HAWROT department of molecular Pharmacology physiology and Biotechnology Brown University Providence Rhode Island 02903 USA

Every cone snail produces a mixture of different conotoxins and secretes them to immobilize their prey and predators. α3/5 Conotoxins, isolated from fish-hunting cone snails, target muscle nicotinic acetylcholine receptors. The structure and function of α3/5 conotoxin from the piscivorous Conus achatinus have not been studied. We synthesized two pentadecamer peptides, Ac 1.1 a and Ac 1.1 b, with appropriate disulfide bonding, based on cDNA sequences of α3/5 conotoxins from C. achatinus. Ac 1.1 a and Ac 1.1 b differ by only one amino acid residue. They have similar potency on blocking recombinant mouse muscle acetylcholine receptor expressed in Xenopus laevis oocytes, with IC50values of 36 nM and 26 nM, respectively. For Ac 1.1b, deletion of the first three N-terminal amino acids did not change its activity, indicating that the Nterminus is not involved in the interaction with its receptor. Furthermore, our experiments indicate that both toxins strongly prefer the α1-δ subunit interface instead of the α1-γ binding site on the mouse muscle nicotinic acetylcholine receptor. These peptides provide additional tools for the study of the structure and function of nicotinic receptor.

关键词： cone snail α3/5 conotoxin disulfide bond nicotinic acetylcholine receptor

Demystifying Mechanosensitive Piezo Ion Channels

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Neuroscience Bulletin 2016年第3期32卷 307-309页

作者： X.Z.Shawn Xu Life Sciences Institute and department of molecular and Integrative physiology University of Michigan

Mechanosensitive channels mediate touch,hearing,proprioception,and blood pressure *** proteins,including Piezo1 and Piezo2,represent a new class of mechanosensitive channels that have been reported to play key roles in most,if not all,of these *** structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels,however,remain *** new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

关键词： Mechanosensation Mechanosensory echanotransduction Mechanical Cryo-EM Piezo