NeuroMolecular Medicine最新文献_第4页

The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis 肠源性短链脂肪酸在多发性硬化症中的作用

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-17 DOI: 10.1007/s12017-024-08783-4

Mohamed J. Saadh, Hani Moslem Ahmed, Zaid Khalid Alani, Rafil Adnan Hussein Al Zuhairi, Zainab M. Almarhoon, Hijaz Ahmad, Mohammed Ubaid, Nathera Hussin Alwan

{"title":"The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis","authors":"Mohamed J. Saadh, Hani Moslem Ahmed, Zaid Khalid Alani, Rafil Adnan Hussein Al Zuhairi, Zainab M. Almarhoon, Hijaz Ahmad, Mohammed Ubaid, Nathera Hussin Alwan","doi":"10.1007/s12017-024-08783-4","DOIUrl":"https://doi.org/10.1007/s12017-024-08783-4","url":null,"abstract":"Multiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as short-chain fatty acids (SCFAs). These molecules may serve as vital molecular signals or metabolic substances regulating host cellular metabolism in the intricate interplay between microbiota and the host. A current emphasis lies on optimizing the health-promoting attributes of colonic bacteria to mitigate urinary tract issues through dietary management. This review aims to spotlight recent investigations on the impact of SCFAs on immune cells pivotal in MS, the involvement of gut microbiota and SCFAs in MS development, and the considerable influence of probiotics on gastrointestinal disruptions in MS. Comprehending the gut-CNS connection holds promise for the development of innovative therapeutic approaches, particularly probiotic-based supplements, for managing MS.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma 在正常张力青光眼小鼠模型中，通过抑制塌缩素反应介导蛋白 2 磷酸化，药物治疗可减轻视网膜神经节细胞的死亡

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-15 DOI: 10.1007/s12017-024-08778-1

Yuebing Wang, Musukha Mala Brahma, Kazuya Takahashi, Alessandra Nolia Blanco Hernandez, Koki Ichikawa, Syuntaro Minami, Yoshio Goshima, Takayuki Harada, Toshio Ohshima

{"title":"Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma","authors":"Yuebing Wang, Musukha Mala Brahma, Kazuya Takahashi, Alessandra Nolia Blanco Hernandez, Koki Ichikawa, Syuntaro Minami, Yoshio Goshima, Takayuki Harada, Toshio Ohshima","doi":"10.1007/s12017-024-08778-1","DOIUrl":"https://doi.org/10.1007/s12017-024-08778-1","url":null,"abstract":"Normal tension glaucoma (NTG) is a progressive neurodegenerative disease in glaucoma families. Typical glaucoma develops because of increased intraocular pressure (IOP), whereas NTG develops despite normal IOP. As a subtype of open-angle glaucoma, NTG is characterized by retinal ganglion cell (RGC) degeneration, gradual loss of axons, and injury to the optic nerve. The relationship between glutamate excitotoxicity and oxidative stress has elicited great interest in NTG studies. We recently reported that suppressing collapsin response mediator protein 2 (CRMP2) phosphorylation in S522A CRMP2 mutant (CRMP2 KIKI) mice inhibited RGC death in NTG mouse models. This study evaluated the impact of the natural compounds huperzine A (HupA) and naringenin (NAR), which have therapeutic effects against glutamate excitotoxicity and oxidative stress, on inhibiting CMRP2 phosphorylation in mice intravitreally injected with N-methyl-d-aspartate (NMDA) and GLAST mutant mice. Results of the study demonstrated that HupA and NAR significantly reduced RGC degeneration and thinning of the inner retinal layer, and inhibited the elevated CRMP2 phosphorylation. These treatments protected against glutamate excitotoxicity and suppressed oxidative stress, which could provide insight into developing new effective therapeutic strategies for NTG.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF-κB/SLICK Pathway 环形 RNA-GRIN2B 通过靶向 NF-κB/SLICK 通路抑制神经性疼痛

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-10 DOI: 10.1007/s12017-024-08774-5

Kun Wang, Zicong Shen, Xin Peng, Xiaotao Wu, Lu Mao

{"title":"Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF-κB/SLICK Pathway","authors":"Kun Wang, Zicong Shen, Xin Peng, Xiaotao Wu, Lu Mao","doi":"10.1007/s12017-024-08774-5","DOIUrl":"https://doi.org/10.1007/s12017-024-08774-5","url":null,"abstract":"The role of circular RNAs (circRNAs) in neuropathic pain is linked to the fundamental physiological mechanisms involved. However, the exact function of circRNAs in the context of neuropathic pain is still not fully understood. The functional impact of circGRIN2B on the excitability of dorsal root ganglion (DRG) neurons was investigated using siRNA or overexpression technology in conjunction with fluorescence in situ hybridization and whole-cell patch-clamp technology. The therapeutic efficacy of circGRIN2B in treating neuropathic pain was confirmed by assessing the pain threshold in a chronic constrictive injury (CCI) model. The interaction between circGRIN2B and NF-κB was examined through RNA pulldown, RIP, and mass spectrometry assays. CircGRIN2B knockdown significantly affected the action potential discharge frequency and the sodium-dependent potassium current flux (SLICK) in DRG neurons. Furthermore, knockdown of circGRIN2B dramatically reduced the SLICK channel protein and mRNA expression in vivo and in vitro. Our research confirmed the interaction between circGRIN2B and NF-κB. These findings demonstrated that circGRIN2B promotes the transcription of the SLICK gene by binding to NF-κB. In CCI rat models, the overexpression of circGRIN2B has been shown to hinder the progression of neuropathic pain, particularly by reducing mechanical and thermal hyperalgesia. Additionally, this upregulation significantly diminished the levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α in the DRG. Upon reviewing these findings, it was determined that circGRIN2B may mitigate the onset of neuropathic pain by modulating the NF-κB/SLICK pathway.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation CYP46A1 多态性与自杀风险的关系：一项初步调查

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-09 DOI: 10.1007/s12017-024-08779-0

María Fernanda Serna-Rodríguez, Oscar Cienfuegos-Jiménez, Ricardo Martín Cerda-Flores, Iván Alberto Marino-Martínez, Mario Alberto Hernández-Ordoñez, José Alfonso Ontiveros-Sánchez de la Barquera, Antonio Alí Pérez-Maya

{"title":"The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation","authors":"María Fernanda Serna-Rodríguez, Oscar Cienfuegos-Jiménez, Ricardo Martín Cerda-Flores, Iván Alberto Marino-Martínez, Mario Alberto Hernández-Ordoñez, José Alfonso Ontiveros-Sánchez de la Barquera, Antonio Alí Pérez-Maya","doi":"10.1007/s12017-024-08779-0","DOIUrl":"https://doi.org/10.1007/s12017-024-08779-0","url":null,"abstract":"Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002–1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Inhibition of p70 Ribosomal S6 Kinase (S6K1) Reduces Cortical Blood Flow in a Rat Model of Autism-Tuberous Sclerosis 抑制 p70 核糖体 S6 激酶 (S6K1) 可降低自闭症-小脑硬化症大鼠模型的皮质血流量

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-04 DOI: 10.1007/s12017-024-08780-7

Oak Z. Chi, Xia Liu, Harvey Fortus, Guy Werlen, Estela Jacinto, Harvey R. Weiss

{"title":"Inhibition of p70 Ribosomal S6 Kinase (S6K1) Reduces Cortical Blood Flow in a Rat Model of Autism-Tuberous Sclerosis","authors":"Oak Z. Chi, Xia Liu, Harvey Fortus, Guy Werlen, Estela Jacinto, Harvey R. Weiss","doi":"10.1007/s12017-024-08780-7","DOIUrl":"https://doi.org/10.1007/s12017-024-08780-7","url":null,"abstract":"The manifestations of tuberous sclerosis complex (TSC) in humans include epilepsy, autism spectrum disorders (ASD) and intellectual disability. Previous studies suggested the linkage of TSC to altered cerebral blood flow and metabolic dysfunction. We previously reported a significant elevation in cerebral blood flow in an animal model of TSC and autism of young Eker rats. Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin could restore normal oxygen consumption and cerebral blood flow. In this study, we investigated whether inhibiting a component of the mTOR signaling pathway, p70 ribosomal S6 kinase (S6K1), would yield comparable effects. Control Long Evans and Eker rats were divided into vehicle and PF-4708671 (S6K1 inhibitor, 75 mg/kg for 1 h) treated groups. Cerebral regional blood flow (14C-iodoantipyrine) was determined in isoflurane anesthetized rats. We found significantly increased basal cortical (+ 32%) and hippocampal (+ 15%) blood flow in the Eker rats. PF-4708671 significantly lowered regional blood flow in the cortex and hippocampus of the Eker rats. PF-4708671 did not significantly lower blood flow in these regions in the control Long Evans rats. Phosphorylation of S6-Ser240/244 and Akt-Ser473 was moderately decreased in Eker rats but only the latter reached statistical significance upon PF-4708671 treatment. Our findings suggest that moderate inhibition of S6K1 with PF-4708671 helps to restore normal cortical blood flow in Eker rats and that this information might have therapeutic potential in tuberous sclerosis complex and autism.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Tetramethylpyrazine Nitrone Promotes the Clearance of Alpha-Synuclein via Nrf2-Mediated Ubiquitin–Proteasome System Activation 四甲基吡嗪硝酮通过 Nrf2 介导的泛素-蛋白酶体系统激活促进α-突触核蛋白的清除

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-03 DOI: 10.1007/s12017-024-08775-4

Baojian Guo, Chengyou Zheng, Jie Cao, Xiaoling Qiu, Fangcheng Luo, Haitao Li, Simon Mingyuan Lee, Xifei Yang, Gaoxiao Zhang, Yewei Sun, Zaijun Zhang, Yuqiang Wang

{"title":"Tetramethylpyrazine Nitrone Promotes the Clearance of Alpha-Synuclein via Nrf2-Mediated Ubiquitin–Proteasome System Activation","authors":"Baojian Guo, Chengyou Zheng, Jie Cao, Xiaoling Qiu, Fangcheng Luo, Haitao Li, Simon Mingyuan Lee, Xifei Yang, Gaoxiao Zhang, Yewei Sun, Zaijun Zhang, Yuqiang Wang","doi":"10.1007/s12017-024-08775-4","DOIUrl":"https://doi.org/10.1007/s12017-024-08775-4","url":null,"abstract":"Aggregation of α-synuclein (α-syn) and α-syn cytotoxicity are hallmarks of sporadic and familial Parkinson’s disease (PD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent enhancement of the expression of the 20S proteasome core particles (20S CPs) and regulatory particles (RPs) increases proteasome activity, which can promote α-syn clearance in PD. Activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) may reduce oxidative stress by strongly inducing Nrf2 gene expression. In the present study, tetramethylpyrazine nitrone (TBN), a potent-free radical scavenger, promoted α-syn clearance by the ubiquitin–proteasome system (UPS) in cell models overexpressing the human A53T mutant α-syn. In the α-syn transgenic mice model, TBN improved motor impairment, decreased the products of oxidative damage, and down-regulated the α-syn level in the serum. TBN consistently up-regulated PGC-1α and Nrf2 expression in tested models of PD. Additionally, TBN similarly enhanced the proteasome 20S subunit beta 8 (Psmb8) expression, which is linked to chymotrypsin-like proteasome activity. Furthermore, TBN increased the mRNA levels of both the 11S RPs subunits Pa28αβ and a proteasome chaperone, known as the proteasome maturation protein (Pomp). Interestingly, specific siRNA targeting of Nrf2 blocked TBN’s effects on Psmb8, Pa28αβ, Pomp expression, and α-syn clearance. In conclusion, TBN promotes the clearance of α-syn via Nrf2-mediated UPS activation, and it may serve as a potentially disease-modifying therapeutic agent for PD.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Acetylation of c-Myc at Lysine 148 Protects Neurons After Ischemia. c-Myc 赖氨酸 148 处的乙酰化可保护缺血后的神经元。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-03-28 DOI: 10.1007/s12017-024-08777-2

V V Guzenko, S S Bachurin, V A Dzreyan, A M Khaitin, Y N Kalyuzhnaya, S V Demyanenko

{"title":"Acetylation of c-Myc at Lysine 148 Protects Neurons After Ischemia.","authors":"V V Guzenko, S S Bachurin, V A Dzreyan, A M Khaitin, Y N Kalyuzhnaya, S V Demyanenko","doi":"10.1007/s12017-024-08777-2","DOIUrl":"10.1007/s12017-024-08777-2","url":null,"abstract":"This study focuses on understanding the role of c-Myc, a cancer-associated transcription factor, in the penumbra following ischemic stroke. While its involvement in cell death and survival is recognized, its post-translational modifications, particularly acetylation, remain understudied in ischemia models. Investigating these modifications could have significant clinical implications for controlling c-Myc activity in the central nervous system. Although previous studies on c-Myc acetylation have been limited to non-neuronal cells, our research examines its expression in perifocal cells during stroke recovery to explore regulatory mechanisms via acetylation. We found that in peri-infarct neurons, c-Myc is upregulated with acetylation at K148 but not K323 during the acute phase of stroke, with SIRT2 deacetylase primarily affecting K148 acetylation. Molecular dynamics simulations suggest that lysine 148 plays a crucial role in stabilizing c-Myc spatial structure. Increased acetylation at K148 reduces c-Myc compaction, potentially limiting its nuclear penetration, promoting calpain-mediated cleavage, and decreasing nuclear localization. Additionally, cytoplasmic acetylation at K148 may alter c-Myc's interaction with unidentified proteins, potentially influencing its pro-apoptotic effects and promoting cytoplasmic accumulation. Targeting SIRT2 with selective inhibitors could be a promising avenue for future stroke therapy strategies.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

An Emerging Role for Enhancer RNAs in Brain Disorders 增强子 RNA 在脑部疾病中的新作用

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-03-28 DOI: 10.1007/s12017-024-08776-3

Ankit Patel, Ashutosh Dharap

{"title":"An Emerging Role for Enhancer RNAs in Brain Disorders","authors":"Ankit Patel, Ashutosh Dharap","doi":"10.1007/s12017-024-08776-3","DOIUrl":"https://doi.org/10.1007/s12017-024-08776-3","url":null,"abstract":"Noncoding DNA undergoes widespread context-dependent transcription to produce noncoding RNAs. In recent decades, tremendous advances in genomics and transcriptomics have revealed important regulatory roles for noncoding DNA elements and the RNAs that they produce. Enhancers are one such element that are well-established drivers of gene expression changes in response to a variety of factors such as external stimuli, cellular responses, developmental cues, and disease states. They are known to act at long distances, interact with multiple target gene loci simultaneously, synergize with other enhancers, and associate with dynamic chromatin architectures to form a complex regulatory network. Recent advances in enhancer biology have revealed that upon activation, enhancers transcribe long noncoding RNAs, known as enhancer RNAs (eRNAs), that have been shown to play important roles in enhancer-mediated gene regulation and chromatin-modifying activities. In the brain, enhancer dysregulation and eRNA transcription has been reported in numerous disorders from acute injuries to chronic neurodegeneration. Because this is an emerging area, a comprehensive understanding of eRNA function has not yet been achieved in brain disorders; however, the findings to date have illuminated a role for eRNAs in activity-driven gene expression and phenotypic outcomes. In this review, we highlight the breadth of the current literature on eRNA biology in brain health and disease and discuss the challenges as well as focus areas and strategies for future in-depth research on eRNAs in brain health and disease.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140314653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Probable Novel APP Met671Leu Mutation in a Chinese Han Family with Early-Onset Alzheimer’s Disease 一个中国汉族早老性痴呆症家族中可能出现的新型 APP Met671Leu 基因突变

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-03-19 DOI: 10.1007/s12017-023-08770-1

Limin Ma, Fengyu Wang, Shuai Chen, Shenghui Wang, Zhenzhen Wang, Mingrong Xia, Yongli Li, Huimin Ma, Junkui Shang, Jiewen Zhang

{"title":"Probable Novel APP Met671Leu Mutation in a Chinese Han Family with Early-Onset Alzheimer’s Disease","authors":"Limin Ma, Fengyu Wang, Shuai Chen, Shenghui Wang, Zhenzhen Wang, Mingrong Xia, Yongli Li, Huimin Ma, Junkui Shang, Jiewen Zhang","doi":"10.1007/s12017-023-08770-1","DOIUrl":"https://doi.org/10.1007/s12017-023-08770-1","url":null,"abstract":"Familial Alzheimer’s disease (AD) is a rare disease caused by autosomal-dominant mutations. APP (encoding amyloid precursor protein), PSEN1 (encoding presenilin 1), and PSEN2 (encoding presenilin 2) are the most common genes cause dominant inherited AD. This study aimed to demonstrate a Chinese early-onset AD pedigree presenting as progressive memory impairment, apraxia, visual-spatial disorders, psychobehavioral disorders, and personality changes with a novel APP gene mutation. The family contains four patients, three carries and three normal family members. The proband underwent brain magnetic resonance imaging (MRI), 18F-fludeoxyglucose positron emission tomography (18F-FDG-PET), cerebrospinal fluid amyloid detection, 18F-florbetapir (AV-45) Positron Emission Computed Tomography (PET) imaging, whole-exome sequencing and Sanger sequencing. Brain MRI images showed brain atrophy, especially in the entorhinal cortex, temporal hippocampus, and lateral ventricle dilation. The FDG-PET showed hypometabolism in the frontotemporal, parietal, and hippocampal regions. 18F-florbetapir (AV-45) PET imaging showed cerebral cortex Aβ protein deposition. The cerebrospinal fluid amyloid protein test showed Aβ42/Aβ40 ratio decreases, pathological phosphor-tau level increases. Whole-exome sequencing detected a new missense mutation of codon 671 (M671L), which was a heterozygous A to T point mutation at position 2011 (c.2011A > T) in exon 16 of the amyloid precursor protein, resulting in the replacement of methionine to Leucine. The co-separation analysis was validated in this family. The mutation was found in 3 patients, 3 clinical normal members in the family, but not in the other 3 unaffected family members, 100 unrelated normal subjects, or 100 sporadic patients with AD. This mutation was probably pathogenic and novel in a Chinese Han family with early-onset AD.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140168161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients. MiR206和423-3p在肌萎缩侧索硬化症快速进展期和缓慢进展期患者中的调制方式不同

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-03-15 DOI: 10.1007/s12017-024-08773-6

Antonio Musarò, Gabriella Dobrowolny, Chiara Cambieri, Laura Libonati, Federica Moret, Irene Casola, Gaia Laurenzi, Matteo Garibaldi, Maurizio Inghilleri, Marco Ceccanti

{"title":"MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients.","authors":"Antonio Musarò, Gabriella Dobrowolny, Chiara Cambieri, Laura Libonati, Federica Moret, Irene Casola, Gaia Laurenzi, Matteo Garibaldi, Maurizio Inghilleri, Marco Ceccanti","doi":"10.1007/s12017-024-08773-6","DOIUrl":"10.1007/s12017-024-08773-6","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease with a wide disease progression. Despite several efforts to develop efficient biomarkers, many concerns about the available ones still need to be addressed. MicroRNA (miR) are non-coding RNAs that can modulate molecular circuits and are involved in ALS pathogenic mechanisms. 22 fast and 23 slow-progressing-defined ALS patients were recruited. ALSFRS-R, strength, respiratory function, nerve conduction studies, and creatine kinase were evaluated at the baseline and after 6 months of follow-up. The mean monthly reduction of the previous variables (progression index - PI) was calculated. MiR206, 133a-3p, 151a-5p, 199a-5p, and 423-3p were dosed. The univariate analysis showed an independent reduction of miR206 and an increase of miR423-3p in patients with a slow slope of ALSFRS-R and weakness, respectively. MiR206 and 423-3p are differently modulated in fast and slow-progressing ALS patients, suggesting a role for microRNAs in prognosis and therapeutic target.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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