Open Biology最新文献_第8页

Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders. 血清淀粉样蛋白 P 成分作为神经退行性疾病药物靶点的遗传学证据。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-07-01 Epub Date: 2024-07-17 DOI: 10.1098/rsob.230419

A Floriaan Schmidt, Chris Finan, Sandesh Chopade, Stephan Ellmerich, Martin N Rossor, Aroon D Hingorani, Mark B Pepys

{"title":"Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders.","authors":"A Floriaan Schmidt, Chris Finan, Sandesh Chopade, Stephan Ellmerich, Martin N Rossor, Aroon D Hingorani, Mark B Pepys","doi":"10.1098/rsob.230419","DOIUrl":"10.1098/rsob.230419","url":null,"abstract":"The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral Aβ amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted cis-Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11, p = 1.8 × 10-3), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59, p = 1.5 × 10-5) and plasma tau concentration (0.06 log2(ng l-1) 95%CI 0.03; 0.08, p = 4.55 × 10-6). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 7","pages":"230419"},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel FAM83G variant from palmoplantar keratoderma patient disrupts WNT signalling via loss of FAM83G-CK1α interaction. 来自掌跖角化症患者的新型 FAM83G 变体通过 FAM83G-CK1α 相互作用的缺失破坏了 WNT 信号。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-07-01 Epub Date: 2024-07-24 DOI: 10.1098/rsob.240075

Lorraine Glennie, Marta Codina Solà, Mar Xunclà, Gloria Aparicio Español, Elena Garcia-Arumí, Eduardo Fidel Tizzano, Nicola T Wood, Thomas J Macartney, Amaia Lasa-Aranzasti, Gopal P Sapkota

{"title":"A novel FAM83G variant from palmoplantar keratoderma patient disrupts WNT signalling via loss of FAM83G-CK1α interaction.","authors":"Lorraine Glennie, Marta Codina Solà, Mar Xunclà, Gloria Aparicio Español, Elena Garcia-Arumí, Eduardo Fidel Tizzano, Nicola T Wood, Thomas J Macartney, Amaia Lasa-Aranzasti, Gopal P Sapkota","doi":"10.1098/rsob.240075","DOIUrl":"10.1098/rsob.240075","url":null,"abstract":"Palmoplantar keratoderma (PPK) is a multi-faceted skin disorder characterized by the thickening of the epidermis and abrasions on the palms and soles of the feet. Among the genetic causes, biallelic pathogenic variants in the FAM83G gene have been associated with PPK in dogs and humans. Here, a novel homozygous variant (c.794G>C, p.Arg265Pro) in the FAM83G gene, identified by whole exome sequencing in a 60-year-old female patient with PPK, is reported. The patient exhibited alterations in the skin of both hands and feet, dystrophic nails, thin, curly and sparse hair, long upper eyelid eyelashes, and poor dental enamel. FAM83G activates WNT signalling through association with ser/thr protein kinase CK1α. When expressed in FAM83G-/- DLD1 colorectal cancer cells, the FAM83GR265P variant displayed poor stability, a loss of interaction with CK1α and attenuated WNT signalling response. These defects persisted in skin fibroblast cells derived from the patient. Our findings imply that the loss of FAM83G-CK1α interaction and subsequent attenuation of WNT signalling underlie the pathogenesis of PPK caused by the FAM83GR265P variant.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 7","pages":"240075"},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A conserved phenylalanine motif among teleost fish provides insight for improving electromagnetic perception. 远洋鱼类中保守的苯丙氨酸基团为改善电磁感知提供了启示。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-07-01 Epub Date: 2024-07-24 DOI: 10.1098/rsob.240092

Brianna Ricker, E Alejandro Castellanos Franco, Gustavo de Los Campos, Galit Pelled, Assaf A Gilad

{"title":"A conserved phenylalanine motif among teleost fish provides insight for improving electromagnetic perception.","authors":"Brianna Ricker, E Alejandro Castellanos Franco, Gustavo de Los Campos, Galit Pelled, Assaf A Gilad","doi":"10.1098/rsob.240092","DOIUrl":"10.1098/rsob.240092","url":null,"abstract":"Magnetoreceptive biology as a field remains relatively obscure; compared with the breadth of species believed to sense magnetic fields, it remains under-studied. Here, we present grounds for the expansion of magnetoreception studies among teleosts. We begin with the electromagnetic perceptive gene (EPG) from Kryptopterus vitreolus and expand to identify 72 teleosts with homologous proteins containing a conserved three-phenylalanine (3F) motif. Phylogenetic analysis provides insight as to how EPG may have evolved over time and indicates that certain clades may have experienced a loss of function driven by different fitness pressures. One potential factor is water type with freshwater fish significantly more likely to possess the functional motif version (FFF), and saltwater fish to have the non-functional variant (FXF). It was also revealed that when the 3F motif from the homologue of Brachyhypopomus gauderio (B.g.) is inserted into EPG-EPG(B.g.)-the response (as indicated by increased intracellular calcium) is faster. This indicates that EPG has the potential to be engineered to improve upon its response and increase its utility to be used as a controller for specific outcomes.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 7","pages":"240092"},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli. 缺乏 Bmal1 会导致节奏性发生变化，并损害对自然刺激的动机。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-07-01 Epub Date: 2024-07-24 DOI: 10.1098/rsob.240051

Paula Berbegal-Sáez, Ines Gallego-Landin, Javier Macía, Laia Alegre-Zurano, Adriana Castro-Zavala, Patrick-Simon Welz, Salvador A Benitah, Olga Valverde

{"title":"Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli.","authors":"Paula Berbegal-Sáez, Ines Gallego-Landin, Javier Macía, Laia Alegre-Zurano, Adriana Castro-Zavala, Patrick-Simon Welz, Salvador A Benitah, Olga Valverde","doi":"10.1098/rsob.240051","DOIUrl":"10.1098/rsob.240051","url":null,"abstract":"Maintaining proper circadian rhythms is essential for coordinating biological functions in mammals. This study investigates the effects of daily arrhythmicity using Bmal1-knockout (KO) mice as a model, aiming to understand behavioural and motivational implications. By employing a new mathematical analysis based on entropy divergence, we identified disrupted intricate activity patterns in mice derived by the complete absence of BMAL1 and quantified the difference regarding the activity oscillation's complexity. Changes in locomotor activity coincided with disturbances in circadian gene expression patterns. Additionally, we found a dysregulated gene expression profile particularly in brain nuclei like the ventral striatum, impacting genes related to reward and motivation. Further investigation revealed that arrhythmic mice exhibited heightened motivation for food and water rewards, indicating a link between circadian disruptions and the reward system. This research sheds light on how circadian clock alterations impact the gene expression regulating the reward system and how this, in turn, can lead to altered seeking behaviour and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 7","pages":"240051"},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential gene expression underpinning the production of distinct sperm morphs in the wax moth Galleria mellonella. 蜡蛾产生不同精子形态的基因表达差异。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-07-01 Epub Date: 2024-07-31 DOI: 10.1098/rsob.240002

Emma Moth, Fiona Messer, Saurabh Chaudhary, Helen White-Cooper

{"title":"Differential gene expression underpinning the production of distinct sperm morphs in the wax moth Galleria mellonella.","authors":"Emma Moth, Fiona Messer, Saurabh Chaudhary, Helen White-Cooper","doi":"10.1098/rsob.240002","DOIUrl":"10.1098/rsob.240002","url":null,"abstract":"Male Lepidoptera produce two distinct sperm types; each ejaculate contains both eupyrene sperm, which can fertilize the egg, and apyrene sperm, which are not fertilization competent. These sperm have distinct morphologies, unique functions and different proteomes. Their production is highly regulated, however, very few genes with specific roles in the production of one or other morph have been described. We present the first comparative transcriptomics study of precursors of eupyrene and apyrene sperm to identify genes potentially implicated in regulating or enacting the distinct differentiation programmes. Differentially expressed genes included genes with potential roles in transcriptional regulation, cell cycle and sperm morphology. We identified gene duplications generating paralogues with functions restricted to one or other morph. However, phylogenetic analysis also revealed evolutionary flexibility in expression patterns of duplicated genes between different lepidopteran species. An improved understanding of lepidopteran reproduction will be vital in targeting prevalent pests in agriculture, and on the flip side, ensuring the fertility and thus survival of pollinator populations in response to environmental stress.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 7","pages":"240002"},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A circle of life: platelet and megakaryocyte cytoskeleton dynamics in health and disease. 生命的轮回：健康和疾病中的血小板和巨核细胞细胞骨架动力学。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-06-01 Epub Date: 2024-06-05 DOI: 10.1098/rsob.240041

Haonan Liu, Julie P I Welburn

{"title":"A circle of life: platelet and megakaryocyte cytoskeleton dynamics in health and disease.","authors":"Haonan Liu, Julie P I Welburn","doi":"10.1098/rsob.240041","DOIUrl":"10.1098/rsob.240041","url":null,"abstract":"Platelets are blood cells derived from megakaryocytes that play a central role in regulating haemostasis and vascular integrity. The microtubule cytoskeleton of megakaryocytes undergoes a critical dynamic reorganization during cycles of endomitosis and platelet biogenesis. Quiescent platelets have a discoid shape maintained by a marginal band composed of microtubule bundles, which undergoes remarkable remodelling during platelet activation, driving shape change and platelet function. Disrupting or enhancing this process can cause platelet dysfunction such as bleeding disorders or thrombosis. However, little is known about the molecular mechanisms underlying the reorganization of the cytoskeleton in the platelet lineage. Recent studies indicate that the emergence of a unique platelet tubulin code and specific pathogenic tubulin mutations cause platelet defects and bleeding disorders. Frequently, these mutations exhibit dominant negative effects, offering valuable insights into both platelet disease mechanisms and the functioning of tubulins. This review will highlight our current understanding of the role of the microtubule cytoskeleton in the life and death of platelets, along with its relevance to platelet disorders.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 6","pages":"240041"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elongation capacity of polyunsaturated fatty acids in the annelid Platynereis dumerilii. 多不饱和脂肪酸在无脊柱藻中的伸长能力

IF 4.5 3区生物学

Open Biology Pub Date : 2024-06-01 Epub Date: 2024-06-12 DOI: 10.1098/rsob.240069

Marc Ramos-Llorens, Khalida Bainour, Leonie Adelmann, Francisco Hontoria, Juan C Navarro, Florian Raible, Óscar Monroig

{"title":"Elongation capacity of polyunsaturated fatty acids in the annelid Platynereis dumerilii.","authors":"Marc Ramos-Llorens, Khalida Bainour, Leonie Adelmann, Francisco Hontoria, Juan C Navarro, Florian Raible, Óscar Monroig","doi":"10.1098/rsob.240069","DOIUrl":"10.1098/rsob.240069","url":null,"abstract":"Elongation of very long-chain fatty acid (Elovl) proteins plays pivotal functions in the biosynthesis of the physiologically essential long-chain polyunsaturated fatty acids (LC-PUFA). Polychaetes have important roles in marine ecosystems, contributing not only to nutrient recycling but also exhibiting a distinctive capacity for biosynthesizing LC-PUFA. To expand our understanding of the LC-PUFA biosynthesis in polychaetes, this study conducted a thorough molecular and functional characterization of Elovl occurring in the model organism Platynereis dumerilii. We identify six Elovl in the genome of P. dumerilii. The sequence and phylogenetic analyses established that four Elovl, identified as Elovl2/5, Elovl4 (two genes) and Elovl1/7, have putative functions in LC-PUFA biosynthesis. Functional characterization confirmed the roles of these elongases in LC-PUFA biosynthesis, demonstrating that P. dumerilii possesses a varied and functionally diverse complement of Elovl that, along with the enzymatic specificities of previously characterized desaturases, enables P. dumerilii to perform all the reactions required for the biosynthesis of the LC-PUFA. Importantly, we uncovered that one of the two Elovl4-encoding genes is remarkably long in comparison with any other animals' Elovl, which contains a C terminal KH domain unique among Elovl. The distinctive expression pattern of this protein in photoreceptors strongly suggests a central role in vision.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 6","pages":"240069"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes. 严重 COVID-19 疾病的风险因素会增加 SARS-CoV-2 对内皮细胞和周细胞的感染性。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-06-01 Epub Date: 2024-06-12 DOI: 10.1098/rsob.230349

Luca Biasetti, Nikos Zervogiannis, Kira Shaw, Harry Trewhitt, Louise Serpell, Dalan Bailey, Edward Wright, Catherine N Hall

{"title":"Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes.","authors":"Luca Biasetti, Nikos Zervogiannis, Kira Shaw, Harry Trewhitt, Louise Serpell, Dalan Bailey, Edward Wright, Catherine N Hall","doi":"10.1098/rsob.230349","DOIUrl":"10.1098/rsob.230349","url":null,"abstract":"Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory disease but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different organs is via the vascular system. We studied the impact of apolipoprotein E (APOE) genotype and inflammation on vascular infectivity by pseudo-typed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse and human cultured endothelial cells and pericytes. Possessing the APOE4 allele or having existing systemic inflammation is known to enhance the severity of COVID-19. Using targeted replacement human APOE3 and APOE4 mice and inflammation induced by bacterial lipopolysaccharide (LPS), we investigated infection by SARS-CoV-2. Here, we show that infectivity was higher in murine cerebrovascular pericytes compared to endothelial cells and higher in cultures expressing APOE4. Furthermore, increasing the inflammatory state of the cells by prior incubation with LPS increased infectivity into human and mouse pericytes and human endothelial cells. Our findings provide insights into the mechanisms underlying severe COVID-19 infection, highlighting how risk factors such as APOE4 genotype and prior inflammation may exacerbate disease severity by augmenting the virus's ability to infect vascular cells.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 6","pages":"230349"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex in Toxoplasma parasites. 弓形虫体内的琥珀酸脱氢酶复合物中，有一种虫体特异性蛋白是必不可少的膜锚定成分。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-06-01 Epub Date: 2024-06-04 DOI: 10.1098/rsob.230463

Soraya M Zwahlen, Jenni A Hayward, Capella S Maguire, Alex R Qin, Giel G van Dooren

{"title":"A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex in Toxoplasma parasites.","authors":"Soraya M Zwahlen, Jenni A Hayward, Capella S Maguire, Alex R Qin, Giel G van Dooren","doi":"10.1098/rsob.230463","DOIUrl":"10.1098/rsob.230463","url":null,"abstract":"Succinate dehydrogenase (SDH) is a protein complex that functions in the tricarboxylic acid cycle and the electron transport chain of mitochondria. In most eukaryotes, SDH is highly conserved and comprises the following four subunits: SdhA and SdhB form the catalytic core of the complex, while SdhC and SdhD anchor the complex in the membrane. Toxoplasma gondii is an apicomplexan parasite that infects one-third of humans worldwide. The genome of T. gondii encodes homologues of the catalytic subunits SdhA and SdhB, although the physiological role of the SDH complex in the parasite and the identity of the membrane-anchoring subunits are poorly understood. Here, we show that the SDH complex contributes to optimal proliferation and O2 consumption in the disease-causing tachyzoite stage of the T. gondii life cycle. We characterize a small membrane-bound subunit of the SDH complex called mitochondrial protein ookinete developmental defect (MPODD), which is conserved among myzozoans, a phylogenetic grouping that incorporates apicomplexan parasites and their closest free-living relatives. We demonstrate that TgMPODD is essential for SDH activity and plays a key role in attaching the TgSdhA and TgSdhB proteins to the membrane anchor of the complex. Our findings highlight a unique and important feature of mitochondrial energy metabolism in apicomplexan parasites and their relatives.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 6","pages":"230463"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs. 解码额颞叶和细胞类型对神经精神疾病和精神活性药物的特异脆弱性。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-06-01 Epub Date: 2024-06-12 DOI: 10.1098/rsob.240063

Jiatong Ji, Honglu Chao, Huimei Chen, Jun Liao, Wenqian Shi, Yangfan Ye, Tian Wang, Yongping You, Ning Liu, Jing Ji, Enrico Petretto

{"title":"Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs.","authors":"Jiatong Ji, Honglu Chao, Huimei Chen, Jun Liao, Wenqian Shi, Yangfan Ye, Tian Wang, Yongping You, Ning Liu, Jing Ji, Enrico Petretto","doi":"10.1098/rsob.240063","DOIUrl":"10.1098/rsob.240063","url":null,"abstract":"Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 6","pages":"240063"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0