Ageing and neurodegenerative diseases最新文献_第2页

Neuropathological insights from SHANK3 mutant animal models SHANK3 突变动物模型的神经病理学启示

Ageing and neurodegenerative diseases Pub Date : 2023-12-28 DOI: 10.20517/and.2023.18

Jia-Wei Zhang, Da-Jian He, Xiao-Jiang Li

{"title":"Neuropathological insights from SHANK3 mutant animal models","authors":"Jia-Wei Zhang, Da-Jian He, Xiao-Jiang Li","doi":"10.20517/and.2023.18","DOIUrl":"https://doi.org/10.20517/and.2023.18","url":null,"abstract":"SHANK3 is a protein primarily found in the postsynaptic density (PSD) of excitatory synapses in the brain. Heterozygous mutations in the shank3 gene have been linked to autism spectrum disorder (ASD) and intellectual disability. There are various animal models carrying mutant SHANK3 that have provided valuable insights into the pathogenesis of ASD. In this review, we will discuss these animal models, with a specific focus on the neuropathology observed in shank3 mouse and monkey models. These models are particularly important as they share closer similarities to humans and are capable of more accurately recapitulating the neuropathological features observed in individuals with ASD. Mice with mutations in the shank3 gene exhibit deficits in social behavior, communication, and repetitive behaviors, which are core features of ASD and support the link between SHANK3 and ASD. However, studies of monkey models with SHANK3 targeting by CRISPR/Cas9 have demonstrated that, unlike mice with completely knocked-out shank3 genes, the monkey model with complete deletion of SHANK3 displays a reduction in the number of neuronal cells. This review discusses the species-specific neuropathology in SHANK3/shank3 knockout mice and monkeys. The differences in neuropathology in SHANK3/shank3 mutant mouse and monkey models suggest that non-human primate models are highly valuable for investigating the mechanism of neurodegeneration that may selectively occur in primate brains.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"23 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139148338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adult-onset idiopathic dystonia: phenotype and mechanism changes “as time goes by” 成人发病型特发性肌张力障碍："随着时间推移 "的表型和机制变化

Ageing and neurodegenerative diseases Pub Date : 2023-12-04 DOI: 10.20517/and.2023.32

Giovanni Defazio, A. Muroni

引用次数: 0

Essential tremor and ageing 特发性震颤和衰老

Ageing and neurodegenerative diseases Pub Date : 2023-10-27 DOI: 10.20517/and.2023.35

Nicki Niemann, Holly A. Shill

引用次数: 0

Unraveling the tau puzzle: a review of mechanistic targets and therapeutic interventions to prevent tau pathology in Alzheimer’s disease 解开tau之谜:在阿尔茨海默病中预防tau病理的机制靶点和治疗干预的综述

Ageing and neurodegenerative diseases Pub Date : 2023-10-27 DOI: 10.20517/and.2023.20

Sachin Kammula, Sulagna Tripathi, Ning Wang, Valina L. Dawson, Ted M. Dawson, Xiaobo Mao

{"title":"Unraveling the tau puzzle: a review of mechanistic targets and therapeutic interventions to prevent tau pathology in Alzheimer’s disease","authors":"Sachin Kammula, Sulagna Tripathi, Ning Wang, Valina L. Dawson, Ted M. Dawson, Xiaobo Mao","doi":"10.20517/and.2023.20","DOIUrl":"https://doi.org/10.20517/and.2023.20","url":null,"abstract":"Alzheimer’s disease (AD) is a prevalent neurodegenerative disease characterized by irreversible neural degeneration and cognitive decline. The prion-like propagation of the β-amyloid (Aβ) and tau proteins leads to the formation of protein plaques and, subsequently, neuronal dysfunction, contributing significantly to AD pathogenesis. Although effective AD treatments remain elusive, targeting tau protein aggregation has emerged as a promising therapeutic approach. However, recent anti-tau antibody trials have shown limited success in improving cognition, underscoring the need for a more advanced, multifaceted approach to address multiple mechanisms of tau pathology. This review examines the role of tau protein in the context of AD, with a particular focus on potential therapeutic interventions. Emphasis is placed on the modulation of tau protein expression, tau post-translational modifications and aggregation, receptor-mediated uptake and extracellular release pathways, neural inflammatory response pathways, intercellular organelle exchange, mitochondrial function, microtubule stability, and nuclear factor expression as critical intervention points. Despite the challenges faced in ongoing anti-tau clinical efforts, a comprehensive strategy targeting multiple pathways involved in tau pathology, by using either combinations of existing drugs or novel multitarget drugs, holds promise. By gaining a deeper understanding of the complex mechanisms underlying tau pathology, researchers can develop innovative therapeutic strategies to combat AD.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"277 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136262063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential effects of Chinese herbs on iron metabolism for the treatment of stroke 中草药对脑卒中铁代谢的潜在影响

Ageing and neurodegenerative diseases Pub Date : 2023-09-20 DOI: 10.20517/and.2023.02

Wen-Juan Guo, Hai-Ling Ding, Qi-Hui Zhang

引用次数: 0

The versatile applications of human pluripotent stem cell-derived microglia and microglia-containing brain organoids 人类多能干细胞衍生的小胶质细胞和含小胶质细胞的脑类器官的广泛应用

Ageing and neurodegenerative diseases Pub Date : 2023-09-07 DOI: 10.20517/and.2023.01

Junjiao Wu, Yu Tang

{"title":"The versatile applications of human pluripotent stem cell-derived microglia and microglia-containing brain organoids","authors":"Junjiao Wu, Yu Tang","doi":"10.20517/and.2023.01","DOIUrl":"https://doi.org/10.20517/and.2023.01","url":null,"abstract":"Microglia are the resident immune cells of the central nervous system (CNS) and play pivotal roles in nervous development, homeostasis, and various neurological diseases. Most of the previous understanding of microglia came from rodents or a limited number of postmortem microglia. However, as significant differences between murine and human microglia have been verified, it has become increasingly apparent that rodents cannot accurately recapitulate human genetics and pathology, thus hindering the translation of microglial findings from rodents to humans. In addition, primary human microglia are notoriously difficult to obtain and lack the scalability required for many high-throughput assays. Fortunately, recent advances in microglia generation from human pluripotent stem cells (hPSCs) have enabled exciting new avenues to decipher or revisit microglial biology in the human context. Given the complex interactions between microglia and other CNS cells, hPSC-derived microglia-like cells (MGLs) were further engrafted within hPSC-derived brain organoids (BOs), which largely lack microglia due to their different embryonic origins, to study human microglial functions in either health and disease state closer to brain microglia. This is a rapidly evolving field, especially in the last five years, that has begun to yield novel insights into the genetics of human microglia and their unique role in neurological diseases. In this review, we will summarize the versatile applications of hPSC-derived MGLs and microglia-containing BOs. Specifically, we will discuss their applications in disease modeling, omics and systematic analysis, interaction with other CNS cell types, as well as transplantation-based human-mouse chimerism.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89392193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of small molecules for disrupting pathological amyloid aggregation in neurodegenerative diseases 神经退行性疾病中破坏病理性淀粉样蛋白聚集的小分子研究进展

Ageing and neurodegenerative diseases Pub Date : 2023-08-29 DOI: 10.20517/and.2023.25

Tianyi Cao, Xiang Li, Dan Li, Youqi Tao

{"title":"Development of small molecules for disrupting pathological amyloid aggregation in neurodegenerative diseases","authors":"Tianyi Cao, Xiang Li, Dan Li, Youqi Tao","doi":"10.20517/and.2023.25","DOIUrl":"https://doi.org/10.20517/and.2023.25","url":null,"abstract":"Neurodegenerative diseases (NDs), encompassing Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are often characterized by the formation of pathological amyloid aggregates, predominantly composed of proteins like amyloid-β, tau, α-synuclein, TDP-43, and others. These amyloid aggregates inflict significant neuronal harm and incite inflammation. This review underscores the potential of small molecules as innovative therapeutic interventions, designed to influence the formation, stability, and breakdown of these pathological amyloid aggregates, which could potentially modify the disease’s progression and minimize its neurotoxic effects. This review first sketches the pathways and mechanisms involved in amyloid aggregation, followed by an in-depth analysis of recent advances in formulating small molecules that directly target these damaging aggregates. This includes various strategies such as inhibiting fibril formation, fostering off-pathway non-toxic oligomers or amorphous aggregates, disaggregating established pathological amyloid fibrils, and enhancing the protein quality control system to combat amyloid aggregation. In the end, this review identifies the challenges and opportunities involved in transitioning these molecules into effective treatments, focusing on critical factors such as penetration of the blood-brain barrier, target specificity, and safety considerations. This review, thus, presents a comprehensive overview of the potential role of small molecules in tackling NDs typified by amyloid aggregation.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86999702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Animal models for research on neurodegenerative diseases 神经退行性疾病研究的动物模型

Ageing and neurodegenerative diseases Pub Date : 2023-08-28 DOI: 10.20517/and.2023.24

Xiao-Jiang Li

引用次数: 0

Immunological, oxidative, and structural factors and their responses to regulatory t lymphocyte therapy in amyotrophic lateral sclerosis 免疫、氧化和结构因素及其对肌萎缩性侧索硬化症调节性t淋巴细胞治疗的反应

Ageing and neurodegenerative diseases Pub Date : 2023-08-23 DOI: 10.20517/and.2023.14

D. Beers, Jason R. Thonhoff, Aaron D. Thome, Alireza Faridar, Weihua Zhao, Shixiang Wen, S. Appel

{"title":"Immunological, oxidative, and structural factors and their responses to regulatory t lymphocyte therapy in amyotrophic lateral sclerosis","authors":"D. Beers, Jason R. Thonhoff, Aaron D. Thome, Alireza Faridar, Weihua Zhao, Shixiang Wen, S. Appel","doi":"10.20517/and.2023.14","DOIUrl":"https://doi.org/10.20517/and.2023.14","url":null,"abstract":"Aim: Amyotrophic lateral sclerosis (ALS) is a systemic disease in which multiple dysfunctional pathways converge, culminating as this devastating disease. Immunological, oxidative, and structural analytes in cross-sectional and longitudinal patient sera samples were investigated and evaluated for their responses following autologous regulatory T lymphocyte (Treg)/IL-2 therapy. \u0000 Methods: This retrospective cohort study was conducted at Houston Methodist Hospital and Massachusetts General Hospital in adults with sporadic ALS. Cross-sectional and longitudinal sera levels for each of the immunological (CCL2, IL-18), oxidative (4-HNE, MDA), and structural analytes (Nf-L, pNf-H) were assayed by ELISAs, and correlated with disease progression and clinical outcomes. \u0000 Results: CCL2 and IL-18 levels were elevated in patients, especially rapidly progressing patients. 4-HNE was elevated in a subset of patients, whereas MDA was elevated in cross-sectional and longitudinally studied subjects. Nf-L was elevated in rapidly progressing patients, whereas pNf-H was decreased in these same patients. In the eleven patients assayed longitudinally, only three patients had increased levels of Nf-L or pNf-H; no patient had increased levels of both neurofilaments. Treg/IL-2 therapy suppressed levels of CCL2, IL-18, and 4-HNE. \u0000 Conclusions: In these cohorts of patients with sporadic ALS, CCL2, IL-18, and 4-HNE accurately reflected disease progression on and off therapy; MDA was elevated but did not respond to therapy. The cross-sectional and longitudinal data were complementary. Nf-L and pNf-H did not reliably and consistently reflect disease progression. Immunological and oxidative pathological factors accurately reflected therapeutic responses in these pathways and are candidates to target clinical trial endpoints.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82065524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Research progress on the role of PGC1α in mitochondrial dysfunction associated with Alzheimer’s disease PGC1α在阿尔茨海默病相关线粒体功能障碍中的作用研究进展

Ageing and neurodegenerative diseases Pub Date : 2023-07-31 DOI: 10.20517/and.2023.04

Zhi-qiang Li, Han Lin, Xiao-ping Huang, Shen-Qing Zhang, Xiao Shu, Xinan Wu

{"title":"Research progress on the role of PGC1α in mitochondrial dysfunction associated with Alzheimer’s disease","authors":"Zhi-qiang Li, Han Lin, Xiao-ping Huang, Shen-Qing Zhang, Xiao Shu, Xinan Wu","doi":"10.20517/and.2023.04","DOIUrl":"https://doi.org/10.20517/and.2023.04","url":null,"abstract":"The transcriptional coactivator Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC1α) holds significant importance in the regulation of mitochondrial function during the pathogenesis of Alzheimer’s Disease (AD). PGC1α is highly expressed in the brain and has the ability to upregulate mitochondrial biogenesis. It modulates various metabolic pathways, such as the β-oxidation of fatty acids, which is important for generating ATP, and glycolysis, which supplies energy and protects against oxidative stress. The dysregulation of PGC1α can lead to alterations in energy metabolism in the brain, involving mitochondrial dysfunction and consequently decreasing cognitive function and neuronal pathologies. In the early stage of AD, the little amyloid-β protein (Aβ) induces the production of ROS, which upregulates the expression of PGC1α, resulting in increasing mitochondrial biogenesis, fatty acid oxidation and its mRNA expression. However, with the development of AD, a load of Aβ and neurofibrillary tangles ultimately lead to mitochondrial dysfunction, impaired mitochondrial respiration, reduced ATP production, and affect the behavioral brain function in AD. It provides a new idea for improvement or treatment of AD symptoms by activating PGC1α.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75985454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0