Translational Neurodegeneration最新文献

{"title":"Nootropic foods in neurodegenerative diseases: mechanisms, challenges, and future.","authors":"Le Anh Minh Nguyen, Courtney Wayne Simons, Raymond Thomas","doi":"10.1186/s40035-025-00476-7","DOIUrl":"10.1186/s40035-025-00476-7","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs) such as Alzheimer's and Parkinson's disease are increasing globally and represent a significant cause of age-related death in the population. Recent studies emphasize the strong association between environmental stressors, particularly dietary factors, and brain health and neurodegeneration unsatisfactory outcomes. Despite ongoing efforts, the efficiency of current treatments for NDDs remains wanting. Considering this, nootropic foods with neuroprotective effects are of high interest as part of a possible long-term therapeutic strategy to improve brain health and alleviate NDDs. However, since it is a new and emerging area in food and neuroscience, there is limited information on mechanisms and challenges to consider for this to be a successful intervention. Here, we seek to address these gaps by presenting a comprehensive review of possible pathways or mechanisms including mutual interactions governing nootropic food metabolism, linkages of the pathways with NDDs, intake, and neuroprotective properties of nootropic foods. We also discuss in-depth intervention with nootropic compounds and dietary patterns in NDDs, providing a detailed exploration of their mechanisms of action. Additionally, we analyze the demand, challenges, and future directions for successful development of nootropic foods targeting NDDs.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"17"},"PeriodicalIF":10.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773257","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":"Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.","authors":"Bryan Sun, Lulin Li, Odette A Harris, Jian Luo","doi":"10.1186/s40035-025-00478-5","DOIUrl":"10.1186/s40035-025-00478-5","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) has emerged as a significant risk factor for Alzheimer's disease (AD), a complex and devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Both conditions share a common feature: blood‒brain barrier (BBB) dysfunction, which is believed to play a pivotal role in linking TBI to the development of AD. This review delves into the intricate relationship between TBI and AD, with a focus on BBB dysfunction and its critical role in disease mechanisms and therapeutic development. We first present recent evidence from epidemiological studies highlighting the increased incidence of AD among individuals with a history of TBI, as well as pathological and animal model studies that demonstrate how TBI can accelerate AD-like pathology. Next, we explore the mechanisms by which BBB dysfunction may mediate TBI-induced AD pathology. Finally, we investigate the shared molecular pathways associated with BBB dysfunction in both TBI and AD conditions and discuss the latest findings on how targeting these pathways and employing regenerative approaches, such as stem cell therapy and pharmacological interventions, can enhance BBB function and mitigate neurodegeneration.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"16"},"PeriodicalIF":10.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721582","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":"Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.","authors":"Yunkwon Nam, Soo Jung Shin, Vijay Kumar, Jihyeon Won, Sujin Kim, Minho Moon","doi":"10.1186/s40035-025-00479-4","DOIUrl":"10.1186/s40035-025-00479-4","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is not a single-cause disease; rather, it is a complex neurodegenerative disease involving multiple pathological pathways influenced by various risk factors. Aggregation and accumulation of amyloid beta (Aβ) and tau are the most prominent features in the brains of AD patients. Aggregated Aβ and tau exert neurotoxic effects in the central nervous system, contributing to the pathogenesis and progression of AD. They also act synergistically to cause neurodegeneration, resulting in memory loss. In this context, dual inhibition of Aβ and tau aggregation, or dissociation of these two aggregates, is considered promising for AD treatment. Recently, dual inhibitors capable of simultaneously targeting the aggregation and dissociation of both Aβ and tau have been investigated. Specific amino acid domains of Aβ and tau associated with their aggregation/dissociation have been identified. Subsequently, therapeutic agents that prevent aggregation or promote disaggregation by targeting these domains have been identified/developed. In this review, we summarize the major domains and properties involved in Aβ and tau aggregation, as well as the therapeutic effects and mechanisms of agents that simultaneously regulate their aggregation and dissociation. This comprehensive review may contribute to the design and discovery of next-generation dual-targeting drugs for Aβ and tau, potentially leading to the development of more effective therapeutic strategies for AD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"15"},"PeriodicalIF":10.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711388","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":"Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.","authors":"Wenchuan Zhang, Chenxuan Huang, Haiyang Yao, Shangzhi Yang, Zeyidan Jiapaer, Juan Song, Xianli Wang","doi":"10.1186/s40035-025-00471-y","DOIUrl":"10.1186/s40035-025-00471-y","url":null,"abstract":"<p><p>Neurological disorders present considerable challenges in diagnosis and treatment due to their complex and diverse etiology. Retrotransposons are a type of mobile genetic element that are increasingly revealed to play a role in these diseases. This review provides a detailed overview of recent developments in the study of retrotransposons in neurodevelopment, neuroaging, and neurological diseases. Retrotransposons, including long interspersed nuclear elements-1, Alu, SINE-VNTR-Alu, and endogenous retrovirus, play important regulatory roles in the development and aging of the nervous system. They have also been implicated in the pathological processes of several neurological diseases, including Alzheimer's disease, X-linked dystonia-parkinsonism, amyotrophic lateral sclerosis, autism spectrum disorder, and schizophrenia. Retrotransposons provide a new perspective for understanding the molecular mechanisms underlying neurological diseases and provide insights into diagnostic and therapeutic strategies of these diseases.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"14"},"PeriodicalIF":10.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701563","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":"Extracellular PHF-tau modulates astrocyte mitochondrial dynamics and mediates neuronal connectivity.","authors":"Valentin Zufferey, Aatmika Barve, Enea Parietti, Luc Belinga, Audrey Bringaud, Yvan Varisco, Kerstin Fabbri, Francesca Capotosti, Paola Bezzi, Nicole Déglon, Pierre Marquet, Nicolas Preitner, Kevin Richetin","doi":"10.1186/s40035-025-00474-9","DOIUrl":"10.1186/s40035-025-00474-9","url":null,"abstract":"<p><strong>Background: </strong>Tau is an intracellular protein that plays a crucial role in stabilizing microtubules. However, it can aggregate into various forms under pathological conditions and be secreted into the brain parenchyma. While the consequences of tau aggregation within neurons have been extensively studied, the effects of extracellular paired helical filaments of tau (ePHF-tau) on neurons and astrocytes are still poorly understood.</p><p><strong>Methods: </strong>This study examined the effect of human ePHF-tau (2N4R) on primary cultures of rat neuroglia, focusing on changes in neurites or synapses by microscopy and analysis of synaptosome and mitochondria proteomic profiles after treatment. In addition, we monitored the behavior of mitochondria in neurons and astrocytes separately over three days using high-speed imaging and high-throughput acquisition and analysis.</p><p><strong>Results: </strong>ePHF-tau was efficiently cleared by astrocytes within two days in a 3D neuron-astrocyte co-culture model. Treatment with ePHF-tau led to a rapid increase in synaptic vesicle production and active zones, suggesting a potential excitotoxic response. Proteomic analyses of synaptosomal and mitochondrial fractions revealed distinct mitochondrial stress adaptations: astrocytes exhibited elevated mitochondrial biogenesis and turnover, whereas neuronal mitochondria displayed only minor oxidative modifications. In a mixed culture model, overexpression of tau 1N4R specifically in astrocytes triggered a marked increase in mitochondrial biogenesis, coinciding with enhanced synaptic vesicle formation in dendrites. Similarly, astrocyte-specific overexpression of PGC1alpha produced a comparable pattern of synaptic vesicle production, indicating that astrocytic mitochondrial adaptation to ePHF-tau may significantly influence synaptic function.</p><p><strong>Conclusions: </strong>These findings suggest that the accumulation of PHF-tau within astrocytes drives changes in mitochondrial biogenesis, which may influence synaptic regulation. This astrocyte-mediated adaptation to tauopathy highlights the potential role of astrocytes in modulating synaptic dynamics in response to tau stress, opening avenues for therapeutic strategies aimed at astrocytic mechanisms in the context of neurodegenerative diseases.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"13"},"PeriodicalIF":10.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693380","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":"Improving vulnerable Calbindin1^- neurons in the ventral hippocampus rescues tau-induced impairment of episodic memory.","authors":"Huiyang Lei, Jingru Lv, Fuqiang Zhang, Linyu Wei, Kun Shi, Jiale Liu, Ting He, Rui Xiong, Fei Sun, Tongkai Zhong, Jingqi Zhao, Dan Ke, Qun Wang, Peiran Jiang, Ai-Min Bao, Jian-Zhi Wang, Ying Yang","doi":"10.1186/s40035-025-00473-w","DOIUrl":"10.1186/s40035-025-00473-w","url":null,"abstract":"<p><strong>Background: </strong>Intraneuronal accumulation of hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD). Given the significant correlation between tau pathology and memory loss in AD patients, identifying vulnerable brain regions, particularly susceptible neuron types in these regions, will advance our understanding of AD onset and shed light on therapeutic strategies to manage its progression.</p><p><strong>Methods: </strong>Immunofluorescent staining was employed to identify the brain regions and neuron types vulnerable to tau pathology in AD. A combination of chemogenetics, electrophysiological recording, in vivo Ca²⁺ recording, and a modified temporal-order discrimination behavior test was utilized to investigate the toxicity of tau accumulation to susceptible neurons in the dorsal part of the ventral hippocampus. Proteomics, phosphoproteomics, and molecular targeting were used to explore the underlying mechanisms of neuron susceptibility to tau accumulation in AD. The beneficial effects of microtubule affinity regulating kinase 4 (MARK4) knockdown and administration of DEPhosphorylation TArgeting Chimera (DEPTAC) were evaluated in AD mice with tau pathology.</p><p><strong>Results: </strong>In postmortem brains of AD patients, we observed robust accumulation of hyperphosphorylated tau in the anterior hippocampal CA1 region, particularly in its Calbindin1^- (Calb1^-) neurons, as opposed to the posterior hippocampal CA1 region and Calb1⁺ neurons. The susceptibility of Calb1^- neurons to phospho-tau accumulation was also observed in P301L mice, especially in the dorsal part of ventral (anterior in human) hippocampal CA1 (dvCA1). In P301L mice, dvCA1 displayed distinct protein and phosphorylated protein networks compared with dorsal CA1, accompanied by overactivation of MARK4. Overexpressing human tau in Calb1^- neurons in the dvCA1 (dvCA1^Calb1- neurons) specifically impairs the temporal-order discrimination of objects. Meanwhile, tau accumulation significantly inhibited the excitability and firing patterns of dvCA1^Calb1- neurons associated with temporal-order discrimination. Knocking down MARK4 or reducing hyperphosporylated tau via DEPTAC in P301L mice significantly ameliorated AD-like tau pathology in dvCA1^Calb1- neurons and improved temporal-order discrimination of objects.</p><p><strong>Conclusion: </strong>These findings highlight the crucial role of dvCA1^Calb1- neurons in the early stage of tau pathology and demonstrate the potential of targeting phosphorylated tau through MARK4 knockdown or DEPTAC administration to counter the vulnerability of dvCA1^Calb1- neurons and, consequently, ameliorate episodic memory deficits in AD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"12"},"PeriodicalIF":10.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558182","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":"Chronic subthalamic nucleus deep brain stimulation reduces pathological TrkB aggregates in a Parkinson's disease rat model.","authors":"Tobias Petschner, Katarina Hofman, Jia Zhi Chen, Thomas Andreska, Daniel Wolf, Susanne Knorr, Robert Blum, Muthuraman Muthuraman, Uwe Gbureck, Jens Volkmann, Michael Sendtner, Chi Wang Ip","doi":"10.1186/s40035-025-00472-x","DOIUrl":"10.1186/s40035-025-00472-x","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"11"},"PeriodicalIF":10.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469351","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":"Parkinson's disease and glucose metabolism impairment.","authors":"Liangjing Chen, Chunyu Wang, Lixia Qin, Hainan Zhang","doi":"10.1186/s40035-025-00467-8","DOIUrl":"10.1186/s40035-025-00467-8","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disorder. PD patients exhibit varying degrees of abnormal glucose metabolism throughout disease stages. Abnormal glucose metabolism is closely linked to the PD pathogenesis and progression. Key glucose metabolism processes involved in PD include glucose transport, glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, the pentose phosphate pathway, and gluconeogenesis. Recent studies suggest that glucose metabolism is a potential therapeutic target for PD. In this review, we explore the connection between PD and abnormal glucose metabolism, focusing on the underlying pathophysiological mechanisms. We also summarize potential therapeutic drugs related to glucose metabolism based on results from current cellular and animal model studies.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"10"},"PeriodicalIF":10.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442085","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 C. elegans gba-3 gene encodes a glucocerebrosidase that exacerbates α-synuclein-mediated impairments in deletion mutants.","authors":"Ning Liu, Rongzhen Li, Xiaobing Huang, Merja Lakso, Garry Wong","doi":"10.1186/s40035-024-00463-4","DOIUrl":"10.1186/s40035-024-00463-4","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"9"},"PeriodicalIF":10.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411098","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":"AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.","authors":"Daniel Choquet, Patricio Opazo, Hongyu Zhang","doi":"10.1186/s40035-025-00470-z","DOIUrl":"10.1186/s40035-025-00470-z","url":null,"abstract":"<p><p>Over the past two decades, there has been a growing recognition of the physiological importance and pathological implications surrounding the surface diffusion of AMPA receptors (AMPARs) and their diffusional trapping at synapses. AMPAR surface diffusion entails the thermally powered random Brownian lateral movement of these receptors within the plasma membrane, facilitating dynamic exchanges between synaptic and extrasynaptic compartments. This process also enables the activity-dependent diffusional trapping and accumulation of AMPARs at synapses through transient binding to synaptic anchoring slots. Recent research highlights the critical role of synaptic recruitment of AMPARs via diffusional trapping in fundamental neural processes such as the development of the early phases of long-term potentiation (LTP), contextual fear memory, memory consolidation, and sensory input-induced cortical remapping. Furthermore, studies underscore that regulation of AMPAR diffusional trapping is altered across various neurological disease models, including Huntington's disease (HD), Alzheimer's disease (AD), and stress-related disorders like depression. Notably, pharmacological interventions aimed at correcting deficits in AMPAR diffusional trapping have demonstrated efficacy in restoring synapse numbers, LTP, and memory functions in these diverse disease models, despite their distinct pathogenic mechanisms. This review provides current insights into the molecular mechanisms underlying the dysregulation of AMPAR diffusional trapping, emphasizing its role as a converging point for multiple pathological signaling pathways. We propose that targeting AMPAR diffusional trapping represents a promising early therapeutic strategy to mitigate synaptic plasticity and memory deficits in a spectrum of brain disorders, encompassing but not limited to HD, AD, and stress-related conditions. This approach underscores an integrated therapeutic target amidst the complexity of these neurodegenerative and neuropsychiatric diseases.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"8"},"PeriodicalIF":10.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400184","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}