Translational Neurodegeneration最新文献

{"title":"Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.","authors":"Xiaoni Zhan, Gehua Wen, Xu Wu, Jia-Yi Li","doi":"10.1186/s40035-025-00490-9","DOIUrl":"10.1186/s40035-025-00490-9","url":null,"abstract":"<p><p>Synucleinopathies and tauopathies are neurodegenerative disorders characterized by the pathological accumulation of α-synuclein (α-syn) and tau proteins, respectively. These disorders are traditionally managed with symptomatic treatments without addressing the underlying pathologies. Recent advancements in passive immunotherapies, notably the FDA approval of the amyloid-beta (Aβ)-targeting antibody lecanemab, have sparked new hope in directly targeting pathological proteins. However, unlike the extracellular Aβ pathology, immunotherapies aimed at α-syn and tau, which predominantly form intracellular inclusions, face substantial challenges. To date, the therapeutic efficacy of five α-syn and 14 tau antibodies has been assessed in patients with synucleinopathies and tauopathies. These immunizations have demonstrated promising preclinical outcomes in alleviating pathological and behavioral deficits, but have not yielded significant clinical improvements in symptoms or measurable biomarkers. Therefore, a clear understanding of potential causes for the discrepancies between preclinical successes and clinical outcomes is critical for the successful translation of immunotherapy in the future. In this review, we examine existing passive immunotherapeutic strategies targeting α-syn and tau, specifically in patients with Alzheimer's disease and Parkinson's disease. Lessons learned from initial trial failures are also discussed, including refinement of animal models, inclusion and stratification of participants, improvement of clinical evaluations, and development of biomarkers. Given the overlapping pathologies and clinical manifestations of synucleinopathies and tauopathies, we further explore the potential of combined therapies targeting co-pathologies, offering novel insights for future therapeutic development against these neurodegenerative disorders.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"33"},"PeriodicalIF":10.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529709","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":"Deficient AMPK-SENP1-Sirt3 signaling impairs mitochondrial complex I function in Parkinson's disease model.","authors":"Xiaoyu Sun, Jianyi Shen, Yimei Shu, Tianshi Wang, Lu He, Ruinan Shen, Yifan Zhou, Jinke Cheng, Suzhen Lin, Jianqing Ding","doi":"10.1186/s40035-025-00489-2","DOIUrl":"https://doi.org/10.1186/s40035-025-00489-2","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies have revealed increased Parkinson's disease (PD) risk among individuals exposed to pesticides like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP is frequently used to induce PD-like symptoms in research models by disrupting mitochondrial complex I (CI) function and causing dopaminergic neuronal loss in the nigrostriatal region. However, the pathway(s) through which MPTP impairs mitochondrial CI function remain to be elucidated. In this study, we aim to identify the molecular mechanisms through which MPTP modulates CI function and define the specific subunits of mitochondrial CI affected by MPTP.</p><p><strong>Methods: </strong>Male mice encompassing either wild-type Sirt3 or Sirt3 K223R de-SUMOylation mutation, were intraperitoneally injected with either MPTP or saline. In vitro experiments were conducted using the SH-SY5Y cell line with or without the Sirt3 de-SUMOylation mutation. Movement performance, mitochondrial function, and protein acetylation were evaluated.</p><p><strong>Results: </strong>MPTP exposure, both in vitro and in vivo, disrupted the AMPK-SENP1-Sirt3 axis, leading to impairment of mitochondrial function. Specifically, MPTP suppressed activation of AMPK, impeding the entry of SENP1 into the mitochondria. The lack of mitochondrial SENP1 resulted in increased levels of SUMOylated Sirt3, which inhibited its deacetylase activity. This led to a significant increase in the acetylation of CI subunits NDUFS3 and NDUFA5, which resulted in reduced CI activity and inhibition of mitochondrial function, and eventually dopaminergic neuronal death. In this pathway, sustained deSUMOylation mutation of Sirt3 (K223R in mice, K288R in humans) mitigated the impact of MPTP on mitochondrial dysregulation, as well as dopaminergic neuronal death and behavioral deficits.</p><p><strong>Conclusion: </strong>The disordered AMPK-SENP1-Sirt3 pathway plays a crucial role in the MPTP-induced CI dysfunction and PD-like phenotype, which provide valuable insights into the mechanisms of PD pathogenesis.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"34"},"PeriodicalIF":10.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544985","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":"Abnormal α-synuclein binds to synaptotagmin 13, impairing extracellular vesicle release in synucleinopathies.","authors":"Yasuo Miki, Shuji Shimoyama, Makoto T Tanaka, Hanae Kushibiki, Asa Nakahara, Xiaopeng Wen, Masanori Hijioka, Tomoya Kon, Megha Murthy, Tomonori Furukawa, Conceição Bettencourt, Fumiaki Mori, Hiroki Mizukami, Shirushi Takahashi, Mari Tada, Yoshihisa Kitamura, Akiyoshi Kakita, Thomas T Warner, Koichi Wakabayashi","doi":"10.1186/s40035-025-00493-6","DOIUrl":"10.1186/s40035-025-00493-6","url":null,"abstract":"<p><strong>Background: </strong>Despite increasing in vitro research, direct evidence of how abnormal α-synuclein (α-Syn) dysregulates vesicular transport and synaptic function in the human brain is lacking.</p><p><strong>Methods: </strong>We performed a transcriptome analysis using brain tissues from a multiple system atrophy (MSA) mouse model, which develops human α-Syn-positive glial cytoplasmic inclusion-like structures and neuronal cytoplasmic inclusion-like structures after tamoxifen injection. We then performed histologic and biochemical analyses using brain samples from 71 human cases (Parkinson's disease, n = 10; dementia with Lewy bodies [DLB], n = 19; MSA, n = 15; control: n = 27), a human blood sample (control: n = 1), and cultured cells.</p><p><strong>Results: </strong>Based on the transcriptome of the MSA mouse model, we identified 10 vesicular transport proteins, including synaptotagmin 13 (SYT13), that might interact with α-Syn. Immunohistochemistry using human brain samples demonstrated that of the 10 vesicular transport proteins identified in the transcriptome analysis, only SYT13 was incorporated into both Lewy bodies and glial cytoplasmic inclusions. Proximity ligation assays revealed that SYT13 exhibited a higher degree of interactions with phosphorylated α-Syn than with endogenous α-Syn. Immunoprecipitation confirmed that SYT13 bound predominantly to phosphorylated α-Syn, SYT1, and the soluble N-ethylmaleimide-sensitive attachment protein receptor (SNARE) complexes. Filter trap assays revealed interactions between SYT13 and soluble toxic β-sheet-rich α-Syn oligomers. Furthermore, fraction analysis showed a significant increase of SYT13 protein levels at the synapses in DLB and MSA. Notably, a correlation was observed between the levels of SYT13 and aggregated α-Syn at the synapses. SYT13 was observed to regulate extracellular vesicle release in association with SYT1 and the SNARE complexes in SH-SY5Y cells. SYT13 overexpression in SH-SY5Y cells impaired extracellular vesicle release. Consistently, the numbers of extracellular vesicles were significantly reduced in the brain homogenates of DLB and MSA cases compared with those in controls.</p><p><strong>Conclusions: </strong>Abnormal α-Syn impairs extracellular vesicle release through interactions with SYT13 in synucleinopathies. Our findings provide insights into therapeutic strategies for alleviating dysregulations of vesicular transport and synaptic function in patients with synucleinopathies.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"32"},"PeriodicalIF":10.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476820","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":"Pathological α-synuclein elicits granulovacuolar degeneration independent of tau.","authors":"Dylan J Dues, Madalynn L Erb, Alysa Kasen, Naman Vatsa, Erin T Williams, An Phu Tran Nguyen, Michael X Henderson, Darren J Moore","doi":"10.1186/s40035-025-00494-5","DOIUrl":"10.1186/s40035-025-00494-5","url":null,"abstract":"<p><strong>Background: </strong>Pathologic heterogeneity is a hallmark of Lewy body dementia (LBD), yet the impact of Lewy pathology on co-pathologies is poorly understood. Lewy pathology, containing α-synuclein, is often associated with regional tau pathology burden in LBD. Similarly, granulovacuolar degeneration bodies (GVBs) have been associated with tau pathology in Alzheimer's disease. Interestingly, GVBs have been detected in a broad range of neurodegenerative conditions including both α-synucleinopathies and tauopathies. Despite the frequent co-occurrence, little is known about the relationship between α-synuclein, tau, and granulovacuolar degeneration.</p><p><strong>Methods: </strong>We developed a mouse model of limbic-predominant α-synucleinopathy by stereotactic injection of mouse α-synuclein pre-formed fibrils (PFFs) into the basal forebrain. This model was used to investigate the relationship of α-synuclein pathology with tau and GVB formation.</p><p><strong>Results: </strong>Our model displayed widespread α-synuclein pathology with a limbic-predominant distribution. Aberrantly phosphorylated tau accumulated in a subset of α-synuclein inclusion-bearing neurons, often colocalized with lysosomes. Many of these same neurons also contained CHMP2b- and CK1δ-positive granules, established markers of GVBs, which suggests a link between tau accumulation and GVB formation. Despite this observation, GVBs were also detected in tau-deficient mice following PFF injection, suggesting that pathological α-synuclein alone is sufficient to elicit GVB formation.</p><p><strong>Conclusions: </strong>Our findings support that α-synuclein pathology can independently elicit granulovacuolar degeneration. The frequent co-accumulation of tau and GVBs suggests a parallel mechanism of cellular dysfunction. The ability of α-synuclein pathology to drive GVB formation in the absence of tau highlights the broader relevance of this process to neurodegeneration with relevance to the pathobiology of LBD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"31"},"PeriodicalIF":10.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333933","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":"Diagnostic value of the motor band sign in amyotrophic lateral sclerosis: a 7T magnetic resonance imaging study.","authors":"Xunyan Huang, Zhe Zhang, Lin Chen, Shuo Yang, Xinyao Liu, Jingfeng Bi, Zaiqiang Zhang, Yongjun Wang, Ning Wei, Wanlin Zhu, Na Chen, Lin Hua, Yuan Li, Yilong Wang, Jing Jing, Hua Pan","doi":"10.1186/s40035-025-00491-8","DOIUrl":"10.1186/s40035-025-00491-8","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"30"},"PeriodicalIF":10.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317975","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":"Aging-dependent YAP1 reduction contributes to AD pathology by upregulating the Nr4a1-AKT/GSK-3β axis.","authors":"Ling Lei, Yilei Cheng, Anqi Yin, Jian-Min Han, Gang Wu, Fumin Yang, Qi Wang, Jian-Zhi Wang, Rong Liu, Hong-Lian Li, Xiaochuan Wang","doi":"10.1186/s40035-025-00487-4","DOIUrl":"10.1186/s40035-025-00487-4","url":null,"abstract":"<p><strong>Background: </strong>Aging is the greatest risk factor for late-onset Alzheimer's disease (LOAD), which accounts for > 95% of all Alzheimer's disease (AD) cases. Yes-associated protein 1 (YAP1), an aging-dependent protein, is a key element in the classical Hippo-YAP1 pathway mediated by a kinase cascade. Research showed that YAP1 was markedly reduced in the brains of individuals with AD. However, the mechanisms underlying the susceptibility of the Hippo-YAP1 signaling pathway in the context of LOAD remain unclear.</p><p><strong>Methods: </strong>AAV9-YAP1-RNAi was injected into the hippocampi of C57BL/6J mice to establish a YAP1 knockdown model. Overexpression of full-length YAP1 was achieved by injecting AAV9-YAP1 into the hippocampi of SAMP8 mice. To establish the model of knockdown of nuclear receptor subfamily 4 group A member 1 (Nr4a1), AAV9-Nr4a1-RNAi was injected into the hippocampi of SAMP8 mice. In the C57BL/6J mice with YAP1 knockdown, Nr4a1 expression was either knocked down or inhibited with DIM-C to examine the impact of Nr4a1 on tau phosphorylation and cognitive deficits. Primary hippocampal neurons from Sprague-Dawley (SD) rats were infected with lentivirus (LV)-YAP1 to create a YAP1 overexpression model, and Aβ treatment was used to induce neuronal senescence. Protein levels were assessed using immunofluorescence, Western blotting, and ELISA. Animal behavior was evaluated using the Morris water maze test, novel object recognition test, and open field test.</p><p><strong>Results: </strong>YAP1 was reduced in the hippocampus of both aged C57BL/6J mice and SAMP8 AD model mice through Hippo pathway activation, as well as in Aβ-induced senescent neurons. Overexpression of YAP1 in primary neurons significantly mitigated the Aβ-induced neuronal senescence by downregulating several senescence-related genes, including p16 and p53. The levels of phosphorylated AKT/GSK-3β in neurons were increased with overexpression of YAP1 both in vivo and in vitro. Knockdown of YAP1 induced AD-like symptoms and exacerbated cognitive decline in 2-month-old C57BL/6J mice. Injection of AAV9-YAP1 in the brains of SAMP8 mice partially alleviated neuronal senescence and enhanced cognitive function. Notably, genetic knockdown and chemical inhibition of Nr4a1 significantly ameliorated cognitive deficits as well as AD-like pathology in these subjects.</p><p><strong>Conclusions: </strong>These findings reveal an etiopathogenic relationship between aging and AD, which is associated with the YAP1-Nr4a1-AKT/GSK-3β signaling pathway. Our findings provide insight into the therapeutic strategies aimed at delaying brain aging and combating neurodegenerative diseases such as AD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"29"},"PeriodicalIF":10.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226811","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":"A genome-wide RNA interference screening reveals protectiveness of SNX5 knockdown in a Parkinson's disease cell model.","authors":"Matthias Höllerhage, Linghan Duan, Oscar Wing Ho Chua, Claudia Moebius, Svenja H Bothe, Kristina Losse, Rebecca Kotzur, Kristina Lau, Franziska Hopfner, Franziska Richter, Christian Wahl-Schott, Marc Bickle, Günter U Höglinger","doi":"10.1186/s40035-025-00486-5","DOIUrl":"10.1186/s40035-025-00486-5","url":null,"abstract":"<p><strong>Background: </strong>Alpha-synuclein (αSyn) is a major player in the pathophysiology of synucleinopathies, which include Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. To date, there is no disease-modifying therapy available for these synucleinopathies. Furthermore, the intracellular mechanisms by which αSyn confers toxicity are not yet fully understood. Therefore, it is of utmost importance to investigate the pathophysiology of αSyn-induced toxicity in order to identify novel molecular targets for the development of disease-modifying therapies.</p><p><strong>Methods: </strong>We performed the first genome-wide siRNA modifier screening in a human postmitotic neuronal cell model using αSyn-induced toxicity as a read-out. In a multi-step approach, we identified several genes, whose knockdown protected against αSyn-induced toxicity. The main hit was further validated by different methods, including immunofluorescence microscopy, qPCR, and Western blot. Furthermore, the main finding was confirmed in mouse primary neurons.</p><p><strong>Results: </strong>The highest protection was achieved by knockdown of SNX5, which encodes the sorting nexin 5 (SNX5) protein, a component of the retromer complex. The protective efficacy of SNX5 knockdown was confirmed with an independent siRNA system. The protective effect of SNX5 knockdown was further confirmed in primary neurons from transgenic mice, where the knockdown of SNX5 led to amelioration of decrease in synchrony that was observed in untreated and control-siRNA-treated cells. SNX5 protein is a component of the SNX-BAR (Bin/Amphiphysin/Rvs) heterodimer, which is part of the retromer complex. Extracellular αSyn and overexpression of intracellular αSyn led to fragmentation of the trans-Golgi network, which was prevented by SNX5 knockdown that led to confinement of αSyn in early endosomes.</p><p><strong>Conclusion: </strong>In summary, our data suggest that SNX5 plays an important role in the trafficking and toxicity of αSyn. Therefore, SNX5 appears to be a target of therapeutic intervention for synucleinopathies.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"27"},"PeriodicalIF":10.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209518","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":"Alterations in sleep-activity cycles and clock gene expression across the synucleinopathy spectrum.","authors":"Maria Comas, Xavier Vidal, Oliver Rawashdeh, Ronald R Grunstein, Simon J G Lewis, Elie Matar","doi":"10.1186/s40035-025-00492-7","DOIUrl":"10.1186/s40035-025-00492-7","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"28"},"PeriodicalIF":10.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217024","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":"Development of human targeted extracellular vesicles loaded with shRNA minicircles to prevent parkinsonian pathology.","authors":"Maria Izco, Carlos Sola, Martin Schleef, Marco Schmeer, María de Toro, Guglielmo Verona, Estefania Carlos, Alejandro Reinares-Sebastian, Sandra Colina, Maria Eugenia Marzo-Sola, Josune Garcia-Sanmartin, Joaquín Fernández-Irigoyen, Enrique Santamaría, Rodolfo Mugica-Vidal, Javier Blesa, Lydia Alvarez-Erviti","doi":"10.1186/s40035-025-00484-7","DOIUrl":"10.1186/s40035-025-00484-7","url":null,"abstract":"<p><strong>Background: </strong>Neurological disorders are the second leading cause of death and the leading cause of disability in the world. Thus, the development of novel disease-modifying strategies is clearly warranted. We have previously developed a therapeutic approach using mouse targeted rabies virus glycoprotein (RVG) extracellular vesicles (EVs) to deliver minicircles (MCs) expressing shRNA (shRNA-MCs) to induce long-term α-synuclein down-regulation. Although the previous therapy successfully reduced the pathology, the clinical translation was extremely unlikely since they were mouse extracellular vesicles.</p><p><strong>Methods: </strong>To overcome this limitation, we developed a source of human RVG-EVs compatible with a personalized therapy using immature dendritic cells. Human peripheral blood monocytes were differentiated in vitro into immature dendritic cells, which were transfected to express the RVG peptide. RVG-EVs containing shRNA-MCs, loaded by electroporation, were injected intravenously in the α-synuclein performed fibril (PFF) mouse model. Level of α-synuclein, phosphorylated α-synuclein aggregates, dopaminergic neurons and motor function were evaluated 90 days after the treatment. To confirm that EVs derived from patients were suitable as a vehicle, proteomic analysis of EVs derived from control, initial and advanced Parkinson's disease was performed.</p><p><strong>Results: </strong>The shRNA-MCs could be successfully loaded into human RVG-EVs and downregulate α-synuclein in SH-SY5Y cells. Intravenous injection of the shRNA-MC-loaded RVG-EVs induced long-term downregulation of α-synuclein mRNA expression and protein level, decreased α-synuclein aggregates, prevented dopaminergic cell death and ameliorated motor impairment in the α-synuclein PFF mouse model. Moreover, we confirmed that the EVs from PD patients are suitable as a personalized therapeutic vehicle.</p><p><strong>Conclusion: </strong>Our study confirmed the therapeutic potential of shRNA-MCs delivered by human RVG-EVs for long-term treatment of neurodegenerative diseases. These results pave the way for clinical use of this approach.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"26"},"PeriodicalIF":10.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151274","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":"Enhanced serum-based seed amplification assay for detecting propagative α-synuclein seeds in Parkinson's disease.","authors":"Yaoyun Kuang, Hengxu Mao, Wei Dai, Tingting Gan, Hao Lin, Jin Li, Xinling Yang, Pingyi Xu","doi":"10.1186/s40035-025-00488-3","DOIUrl":"10.1186/s40035-025-00488-3","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"24"},"PeriodicalIF":10.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128728","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}