journal
https://read.qxmd.com/read/38037124/neuronal-and-synaptic-adaptations-underlying%C3%A2-the-benefits-of-deep-brain-stimulation-for-parkinson-s-disease
#21
REVIEW
Wenying Xu, Jie Wang, Xin-Ni Li, Jingxue Liang, Lu Song, Yi Wu, Zhenguo Liu, Bomin Sun, Wei-Guang Li
Deep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment...
November 30, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/38012808/n6-methyladenosine-modified-circrims2-mediates-synaptic-and-memory-impairments-by-activating-glun2b-ubiquitination-in-alzheimer-s-disease
#22
JOURNAL ARTICLE
Xiong Wang, Jiazhao Xie, Lu Tan, Yanjun Lu, Na Shen, Jiaoyuan Li, Hui Hu, Huijun Li, Xiaoguang Li, Liming Cheng
BACKGROUND: Synaptic degeneration occurs in the early stage of Alzheimer's disease (AD) before devastating symptoms, strongly correlated with cognitive decline. Circular RNAs (circRNAs) are abundantly enriched in neural tissues, and aberrant expression of circRNAs precedes AD symptoms, significantly correlated with clinical dementia severity. However, the direct relationship between circRNA dysregulation and synaptic impairment in the early stage of AD remains poorly understood. METHODS: Hippocampal whole-transcriptome sequencing was performed to identify dysregulated circRNAs and miRNAs in 4-month-old wild-type and APP/PS1 mice...
November 28, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37968718/a-phase-1-open-label-pilot-study-of-low-dose-interleukine-2-immunotherapy-in-patients-with-alzheimer-s-disease
#23
LETTER
Alireza Faridar, Abdulmunaim M Eid, Aaron D Thome, Weihua Zhao, David R Beers, Maria B Pascual, Mohammad O Nakawah, Gustavo C Roman, Charles S Davis, Michael Grundman, Joseph C Masdeu, Stanley H Appel
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05821153.
November 16, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37964328/oligodendrocyte-progenitor-cells-in-alzheimer-s-disease-from-physiology-to-pathology
#24
REVIEW
Peibin Zou, Chongyun Wu, Timon Cheng-Yi Liu, Rui Duan, Luodan Yang
Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring cells and contributing to the integrity of the blood-brain barrier (BBB). However, under the pathological circumstances of Alzheimer's disease (AD), the brain's microenvironment undergoes detrimental changes that significantly impact OPCs and their functions. Starting with OPC functions, we delve into the transformation of OPCs to myelin-producing oligodendrocytes, the intricate signaling interactions with other cells in the central nervous system (CNS), and the fascinating process of phagocytosis, which influences the function of OPCs and affects CNS homeostasis...
November 14, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37950283/a-novel-transgenic-mouse-line-with-hippocampus-dominant-and-inducible-expression-of-truncated-human-tau
#25
JOURNAL ARTICLE
Yang Gao, Yuying Wang, Huiyang Lei, Zhendong Xu, Shihong Li, Haitao Yu, Jiazhao Xie, Zhentao Zhang, Gongping Liu, Yao Zhang, Jie Zheng, Jian-Zhi Wang
BACKGROUND: Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer's disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking. METHODS: We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368 (termed hTau368), a tau fragment increased in the brains of AD patients and aged mouse brains. Doxycycline (dox) was administered in drinking water to induce hTau368 expression...
November 10, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37946307/intranasal-administration-of-induced-pluripotent-stem-cell-derived-cortical-neural-stem-cell-secretome-as-a-treatment-option-for-alzheimer-s-disease
#26
JOURNAL ARTICLE
Hyunkyung Mo, Juryun Kim, Jennifer Yejean Kim, Jang Woon Kim, Heeju Han, Si Hwa Choi, Yeri Alice Rim, Ji Hyeon Ju
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, resulting in gradual destruction of cognitive abilities. Research on the development of various AD treatments is underway; however, no definitive treatment has been developed yet. Herein, we present induced pluripotent stem cell (iPSC)-derived cortical neural stem cell secretome (CNSC-SE) as a new treatment candidate for AD and explore its efficacy. METHODS: We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation...
November 9, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37915104/nlrp3-inflammasome-in-cognitive-impairment-and-pharmacological-properties%C3%A2-of%C3%A2-its-inhibitors
#27
REVIEW
Yi Xu, Yanling Yang, Xi Chen, Danling Jiang, Fei Zhang, Yao Guo, Bin Hu, Guohai Xu, Shengliang Peng, Lidong Wu, Jialing Hu
Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1β and IL-18) by activating caspase-1...
November 2, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37908010/metabolic-regulation-of-microglial-phagocytosis-implications-for-alzheimer-s-disease-therapeutics
#28
REVIEW
Izabela Lepiarz-Raba, Ismail Gbadamosi, Roberta Florea, Rosa Chiara Paolicelli, Ali Jawaid
Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the central nervous system, including surveillance, phagocytosis and release of a variety of soluble factors. Importantly, a majority of their functions are closely related to changes in their metabolism. This natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic interventions...
October 31, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37828541/janus-kinase-inhibitors-are-potential-therapeutics-for-amyotrophic-lateral-sclerosis
#29
REVIEW
Peter J Richardson, Daniel P Smith, Alex de Giorgio, Xenia Snetkov, Joshua Almond-Thynne, Sara Cronin, Richard J Mead, Christopher J McDermott, Pamela J Shaw
Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells...
October 12, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37730668/pathological-insights-from-amyotrophic-lateral-sclerosis-animal-models-comparisons-limitations-and-challenges
#30
REVIEW
Longhong Zhu, Shihua Li, Xiao-Jiang Li, Peng Yin
In order to dissect amyotrophic lateral sclerosis (ALS), a multigenic, multifactorial, and progressive neurodegenerative disease with heterogeneous clinical presentations, researchers have generated numerous animal models to mimic the genetic defects. Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics. However, most genetically modified rodent models lack overt pathological features, imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms...
September 20, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37726850/patient-derived-ipsc-models-of-friedreich-ataxia-a-new-frontier-for-understanding-disease-mechanisms-and-therapeutic-application
#31
REVIEW
Saumya Maheshwari, Gabriela Vilema-Enríquez, Richard Wade-Martins
Friedreich ataxia (FRDA) is a rare genetic multisystem disorder caused by a pathological GAA trinucleotide repeat expansion in the FXN gene. The numerous drawbacks of historical cellular and rodent models of FRDA have caused difficulty in performing effective mechanistic and translational studies to investigate the disease. The recent discovery and subsequent development of induced pluripotent stem cell (iPSC) technology provides an exciting platform to enable enhanced disease modelling for studies of rare genetic diseases...
September 20, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37718439/role-of-dopamine-in-the-pathophysiology-of-parkinson-s-disease
#32
REVIEW
Zhi Dong Zhou, Ling Xiao Yi, Dennis Qing Wang, Tit Meng Lim, Eng King Tan
A pathological feature of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra pars compacta in PD brains. DA is the neurotransmitter of dopaminergic neurons. Accumulating evidence suggests that DA interacts with environmental and genetic factors to contribute to PD pathophysiology. Disturbances of DA synthesis, storage, transportation and metabolism have been shown to promote neurodegeneration of dopaminergic neurons in various PD models...
September 18, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37697342/research-progress-on-the-role-of-extracellular-vesicles-in-neurodegenerative-diseases
#33
REVIEW
Zhengzhe Li, Xiaoling Wang, Xiaoxing Wang, Xiaomei Yi, Yin Kwan Wong, Jiyang Wu, Fangfang Xie, Die Hu, Qi Wang, Jigang Wang, Tianyu Zhong
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, affect millions of people worldwide. Tremendous efforts have been put into disease-related research, but few breakthroughs have been made in diagnostic and therapeutic approaches. Extracellular vesicles (EVs) are heterogeneous cell-derived membrane structures that arise from the endosomal system or are directly separated from the plasma membrane. EVs contain many biomolecules, including proteins, nucleic acids, and lipids, which can be transferred between different cells, tissues, or organs, thereby regulating cross-organ communication between cells during normal and pathological processes...
September 11, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37667404/large-scale-proximity-extension-assay-reveals-csf-midkine-and-dopa-decarboxylase-as-supportive-diagnostic-biomarkers-for-parkinson-s-disease
#34
JOURNAL ARTICLE
Wojciech Paslawski, Shervin Khosousi, Ellen Hertz, Ioanna Markaki, Adam Boxer, Per Svenningsson
BACKGROUND: There is a need for biomarkers to support an accurate diagnosis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) has been a successful biofluid for finding neurodegenerative biomarkers, and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies. Using a large-scale multiplex proximity extension assay (PEA) approach, we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders (APD)...
September 4, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37635244/early-gcase-activity-is-a-predictor-of-long-term-cognitive-decline-in-parkinson-s-disease
#35
LETTER
Linn Oftedal, Johannes Lange, Kenn Freddy Pedersen, Aleksander Hagen Erga, Ingvild Dalen, Ole-Bjørn Tysnes, Guido Alves, Jodi Maple-Grødem
No abstract text is available yet for this article.
August 28, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37620916/%C3%AE-synuclein-carrying-astrocytic-extracellular-vesicles-in-parkinson-pathogenesis-and-diagnosis
#36
JOURNAL ARTICLE
Pan Wang, Guoyu Lan, Bin Xu, Zhenwei Yu, Chen Tian, Xia Lei, Wassilios G Meissner, Tao Feng, Ying Yang, Jing Zhang
BACKGROUND: The accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders...
August 25, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37596644/the-potential-impact-of-clinical-factors-on-blood-based-biomarkers-for-alzheimer-s-disease
#37
LETTER
Fengfeng Pan, Yan Lu, Qi Huang, Fang Xie, Jingye Yang, Qihao Guo
No abstract text is available yet for this article.
August 18, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37501056/multidimensional-biomarkers-for-multiple-system-atrophy-an-update-and-future-directions
#38
REVIEW
Linlin Wan, Sudan Zhu, Zhao Chen, Rong Qiu, Beisha Tang, Hong Jiang
Multiple system atrophy (MSA) is a fatal progressive neurodegenerative disease. Biomarkers are urgently required for MSA to improve the diagnostic and prognostic accuracy in clinic and facilitate the development and monitoring of disease-modifying therapies. In recent years, significant research efforts have been made in exploring multidimensional biomarkers for MSA. However, currently few biomarkers are available in clinic. In this review, we systematically summarize the latest advances in multidimensional biomarkers for MSA, including biomarkers in fluids, tissues and gut microbiota as well as imaging biomarkers...
July 28, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37496074/clinical-evidence-of-human-pathogens-implicated-in-alzheimer-s-disease-pathology-and-the-therapeutic-efficacy-of-antimicrobials-an-overview
#39
REVIEW
Celso S G Catumbela, Vijayasree V Giridharan, Tatiana Barichello, Rodrigo Morales
A wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer's disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet clear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain...
July 26, 2023: Translational Neurodegeneration
https://read.qxmd.com/read/37468944/animal-models-of-parkinson-s-disease-bridging-the-gap-between-disease-hallmarks-and-research-questions
#40
REVIEW
Axelle Dovonou, Cyril Bolduc, Victoria Soto Linan, Charles Gora, Modesto R Peralta Iii, Martin Lévesque
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains a serious affliction that affects a growing proportion of the population. Prevailing treatments only alleviate symptoms; there is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease. Over the past decades, several animal models have been developed to study PD. Although no model precisely recapitulates the pathology, they still provide valuable information that contributes to our understanding of the disease and the limitations of our treatment options...
July 19, 2023: Translational Neurodegeneration
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