Translational Neurodegeneration最新文献

{"title":"Can exercise benefits be harnessed with drugs? A new way to combat neurodegenerative diseases by boosting neurogenesis.","authors":"Renqing Zhao","doi":"10.1186/s40035-024-00428-7","DOIUrl":"10.1186/s40035-024-00428-7","url":null,"abstract":"<p><p>Adult hippocampal neurogenesis (AHN) is affected by multiple factors, such as enriched environment, exercise, ageing, and neurodegenerative disorders. Neurodegenerative disorders can impair AHN, leading to progressive neuronal loss and cognitive decline. Compelling evidence suggests that individuals engaged in regular exercise exhibit higher production of proteins that are essential for AHN and memory. Interestingly, specific molecules that mediate the effects of exercise have shown effectiveness in promoting AHN and cognition in different transgenic animal models. Despite these advancements, the precise mechanisms by which exercise mimetics induce AHN remain partially understood. Recently, some novel exercise molecules have been tested and the underlying mechanisms have been proposed, involving intercommunications between multiple organs such as muscle-brain crosstalk, liver-brain crosstalk, and gut-brain crosstalk. In this review, we will discuss the current evidence regarding the effects and potential mechanisms of exercise mimetics on AHN and cognition in various neurological disorders. Opportunities, challenges, and future directions in this research field are also discussed.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"36"},"PeriodicalIF":10.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761130","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}

{"title":"Dorsal raphe nucleus-hippocampus serotonergic circuit underlies the depressive and cognitive impairments in 5×FAD male mice.","authors":"Meiqin Chen, Chenlu Wang, Yinan Lin, Yanbing Chen, Wenting Xie, Xiaoting Huang, Fan Zhang, Congrui Fu, Kai Zhuang, Tingting Zou, Dan Can, Huifang Li, Shengxi Wu, Ceng Luo, Jie Zhang","doi":"10.1186/s40035-024-00425-w","DOIUrl":"10.1186/s40035-024-00425-w","url":null,"abstract":"<p><strong>Background: </strong>Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression.</p><p><strong>Methods: </strong>We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model.</p><p><strong>Results: </strong>We found that the activity of dorsal raphe nucleus serotonin neurons (DRN^5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN^5-HT-dCA1^CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN^5-HT-dCA1^CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT_1BR) and 4 (5-HT₄R). Pharmacological activation of 5-HT_1BR or 5-HT₄R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN^5-HT-dCA1^CaMKII neural circuit to improve synaptic plasticity.</p><p><strong>Conclusions: </strong>These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"34"},"PeriodicalIF":10.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752922","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}

{"title":"Ultrasensitive detection of aggregated α-synuclein using quiescent seed amplification assay for the diagnosis of Parkinson's disease.","authors":"Hengxu Mao, Yaoyun Kuang, Du Feng, Xiang Chen, Lin Lu, Wencheng Xia, Tingting Gan, Weimeng Huang, Wenyuan Guo, Hancun Yi, Yirong Yang, Zhuohua Wu, Wei Dai, Hui Sun, Jieyuan Wu, Rui Zhang, Shenqing Zhang, Xiuli Lin, Yuxuan Yong, Xinling Yang, Hongyan Li, Wenjun Wu, Xiaoyun Huang, Zhaoxiang Bian, Hoi Leong Xavier Wong, Xin-Lu Wang, Michael Poppell, Yi Ren, Cong Liu, Wen-Quan Zou, Shengdi Chen, Ping-Yi Xu","doi":"10.1186/s40035-024-00426-9","DOIUrl":"10.1186/s40035-024-00426-9","url":null,"abstract":"<p><strong>Background: </strong>Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson's disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation.</p><p><strong>Methods: </strong>We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023.</p><p><strong>Results: </strong>QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples.</p><p><strong>Conclusion: </strong>We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"35"},"PeriodicalIF":10.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761131","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}

{"title":"Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer's Disease.","authors":"Maria Luisa De Paolis, Ilaria Paoletti, Claudio Zaccone, Fioravante Capone, Marcello D'Amelio, Paraskevi Krashia","doi":"10.1186/s40035-024-00423-y","DOIUrl":"10.1186/s40035-024-00423-y","url":null,"abstract":"<p><p>The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer's Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"33"},"PeriodicalIF":10.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459506","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}

{"title":"Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?","authors":"Rocío Del Carmen Bravo-Miana, Jone Karmele Arizaga-Echebarria, David Otaegui","doi":"10.1186/s40035-024-00418-9","DOIUrl":"10.1186/s40035-024-00418-9","url":null,"abstract":"<p><p>The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"32"},"PeriodicalIF":10.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427623","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}

{"title":"DOPA-decarboxylase is elevated in CSF, but not plasma, in prodromal and de novo Parkinson's disease.","authors":"Ellen Appleton, Shervin Khosousi, Michael Ta, Michael Nalls, Andrew B Singleton, Andrea Sturchio, Ioanna Markaki, Wojciech Paslawski, Hirotaka Iwaki, Per Svenningsson","doi":"10.1186/s40035-024-00421-0","DOIUrl":"10.1186/s40035-024-00421-0","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"31"},"PeriodicalIF":12.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306939","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}

{"title":"Retraction Note: Asiaticoside, a trisaccaride triterpene induces biochemical and molecular variations in brain of mice with parkinsonism","authors":"Uvarajan Sampath, Vanisree Arambakkam Janardhanam","doi":"10.1186/s40035-024-00424-x","DOIUrl":"https://doi.org/10.1186/s40035-024-00424-x","url":null,"abstract":"This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/2047-9158-2-23.","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"41 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253539","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}

{"title":"In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.","authors":"Juan I López-Carbonero, Irene García-Toledo, Laura Fernández-Hernández, Pablo Bascuñana, María J Gil-Moreno, Jordi A Matías-Guiu, Silvia Corrochano","doi":"10.1186/s40035-024-00419-8","DOIUrl":"10.1186/s40035-024-00419-8","url":null,"abstract":"<p><p>TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer's disease, Huntington's disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"29"},"PeriodicalIF":10.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237723","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}

{"title":"Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.","authors":"Miaodan Huang, Yong U Liu, Xiaoli Yao, Dajiang Qin, Huanxing Su","doi":"10.1186/s40035-024-00416-x","DOIUrl":"10.1186/s40035-024-00416-x","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, resulting in global health burden and limited post-diagnosis life expectancy. Although primarily sporadic, familial ALS (fALS) cases suggest a genetic basis. This review focuses on SOD1, the first gene found to be associated with fALS, which has been more recently confirmed by genome sequencing. While informative, databases such as ALSoD and STRENGTH exhibit regional biases. Through a systematic global examination of SOD1 mutations from 1993 to 2023, we found different geographic distributions and clinical presentations. Even though different SOD1 variants are expressed at different protein levels and have different half-lives and dismutase activities, these alterations lead to loss of function that is not consistently correlated with disease severity. Gain of function of toxic aggregates of SOD1 resulting from mutated SOD1 has emerged as one of the key contributors to ALS. Therapeutic interventions specifically targeting toxic gain of function of mutant SOD1, including RNA interference and antibodies, show promise, but a cure remains elusive. This review provides a comprehensive perspective on SOD1-associated ALS and describes molecular features and the complex genetic landscape of SOD1, highlighting its importance in determining diverse clinical manifestations observed in ALS patients and emphasizing the need for personalized therapeutic strategies.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"28"},"PeriodicalIF":10.8,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11138100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176467","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}

{"title":"The relation of synaptic biomarkers with Aβ, tau, glial activation, and neurodegeneration in Alzheimer's disease.","authors":"Yi-Ting Wang, Nicholas J Ashton, Stijn Servaes, Johanna Nilsson, Marcel S Woo, Tharick A Pascoal, Cécile Tissot, Nesrine Rahmouni, Joseph Therriault, Firoza Lussier, Mira Chamoun, Serge Gauthier, Ann Brinkmalm, Henrik Zetterberg, Kaj Blennow, Pedro Rosa-Neto, Andréa L Benedet","doi":"10.1186/s40035-024-00420-1","DOIUrl":"10.1186/s40035-024-00420-1","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"27"},"PeriodicalIF":12.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158019","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}