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Effect of pesticides on phosphorylation of tau protein,and its influence on Alzheimer’s disease

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World Journal of Clinical Cases 2023年第24期11卷 5628-5642页

作者： Erandis D Torres-Sánchez Genaro G Ortiz Emmanuel Reyes-Uribe Juan H Torres-Jasso Joel Salazar-Flores Department of Medical and Life Sciences University Center of la CienegaUniversity of GuadalajaraOcotlan 47820JaliscoMexico Department of Philosophical and Methodological Disciplines and Service of Molecular Biology in Medicine Hospital Civil University of GuadalajaraGuadalajara 44340JaliscoMexico Department of Biological Sciences CUCOSTAUniversity of GuadalajaraPuerto Vallarta 48280JaliscoMexico

Alzheimer’s disease(AD)is a progressive and neurodegenerative illness which results in alterations in cognitive *** is characterized by loss/dysfunction of cholinergic neurons,and formation of amyloid plaques,and formation of neurofibrillary tangles,among other changes,due to hyperphosphorylation of *** to pesticides in humans occurs frequently due to contact with contaminated food,water,or ***,organophosphates,carbamates,pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive *** aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein,and its cognitive implications in the development of *** was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198,Ser199,Ser202,Thr205,Ser396 and *** with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta,and protein ***,it altered the expression of the microtubule associated protein tau gene,and changed levels of intracellular *** changes affected tau protein phosphorylation and neuroinflammation,and also increased oxidative *** addition,the exposed subjects had poor level of performance in tests that involved evaluation of novelty,as test on verbal,non-verbal,spatial memory,attention,and problem-solving skills.

关键词： Organochlorines Organophosphates Carbamates Pyrethroids Neonicotinoids tau protein

Diagnostic Prospectives with tau protein and Imaging Techniques to Detect Development of Chronic Traumatic Encephalopathy

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Journal of Behavioral and Brain Science 2023年第4期13卷 55-65页

作者： Amit Naskar Danielle Jayanty Kimberly Head Gulshan L. Khanna Vatsalya Vatsalya Arpan Banerjee Cognitive Brain Dynamics Lab National Brain Research Centre Manesar India Department of Medicine University of Louisville Louisville KY USA Professor and Pro Vice Chancellor Manav Rachna International Institute of Research and Studies Faridabad India Robley Rex VA Medical Center Louisville KY USA National Institute on Alcohol Abuse and Alcoholism NIH Bethesda MD USA

Brain damage sustained from repeated blows in boxing, wrestling, and other combat sports has serious physical and mental health consequences. The degenerative brain disease, chronic traumatic encephalopathy (CTE), presents clinically with memory loss, aggression, difficulty in rational thinking and other cognitive problems. This spectrum, which mimics Alzheimer’s disease, is diagnosed post-mortem through a brain biopsy in many professional athletes. However, little is known about the process of development and how to identify vulnerable individuals who may be on course for developing CTE. Boxing is a sport that has a severe toll on athletes’ health, primarily on their brain health and function. This review addresses the concerns of brain injury, describes the pathologies that manifest in multiple scales, e.g., molecular and cognitive, and also proposes possible diagnostic and prognostic markers to characterize the early onset of CTE along with the aim to identify a starting point for future precautions and interventions.

关键词： Athletes Axonal Injury tau protein Chronic Traumatic Encephalopathy Traumatic Brain Injury Boxing Wrestling

Green tea polyphenol ameliorates spatial learning and memory impairment and tau protein hyperphosphorylation of hippocampal neurons induced by okadaic acid in rats

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Green tea polyphenol ameliorates spatial learning and memory...

Liquid-Liquid Phase Separation of tau protein Is Encoded at the Monomeric Level

中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Hong-Yu LI~1,Xiu-Kui WU~1,Mei-Jun SHI~1,Jun ZHANG~1,Liu JING~1,De-Zheng GONG~1,Liang ZHU~1,Li-Li GUAN~1,Qiong WU~1,Bo YUAN~1,Guo-Zhu HAN~2,Yuan ZOU~(1,*) 1 Department of Physiology 2 Faculty of Pharmacology,Dalian Medical University,Dalian 116044,China

＜正＞Objective:Green tea polyphenols（GTPs） are now being considered as possible protective agents in neurodegenerative diseases such as Alzheimer’s disease（AD）.Previous studies suggested that GTPs could inhibit amyloid fibril formation and protect neurons from toxicity induced byβ-amyloid in ***,it is still unclear that whether GTPs decrease hyperphosphorylation of tau protein and ameliorate learning and memory impairments induced by okadaic acid（OA） in *** aim of this study is to explore the effects of GTPs on the hyperphosphorylation of tau protein and the learning and memory impairments in ***:SD rats were pretreated with GTPs by intragastric administration,and microinjected with OA into the right dorsal *** ethological test was examined,and hyperphosphorylation of tau protein was examined both in vivo and in ***: With the increase of training,the escape latency of each group shortened gradually,and that of rats with GTPs shortened more obviously than control *** staying time in the target quadrant was significantly decreased after OA microinjection,whereas rats pretreated with GTPs stayed for longer time,and had a longer swimming distance in target quadrant compared with control group ***,GTPs could greatly attenuate the loss of primary hippocampal neurons and inhibit neurite degeneration induced by OA-induced toxicity,and also reduce the accumulation of PHF-13-positve ***:These results suggested that GTPs could ameliorate OA-induced spatial memory impairment and diminish tau *** had protective effects against OA-induced *** data indicated that green tea may be beneficial for preventing AD.

关键词： green tea polyphenols tau protein okadaic acid Alzheimer’s disease

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Liquid-Liquid Phase Separation of Tau Protein Is Encoded at ...

Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer‑like social memory loss

2021年全国生物相分离和相变学术研讨会

作者： Xuewei Dong Yiming Tang Guanghong Wei Department of Physics Fudan University

Liquid-liquid phase separation(LLPS) is involved in both physiological and pathological *** intrinsically disordered protein tau and its K18 construct can undergo LLPS in a distinct temperature-dependent manner,and the LLPS of tau protein can initiate tau ***,the underlying mechanism driving tau LLPS remains largely *** understand the temperature-dependent LLPS behavior of tau at the monomeric level,we explored the conformational ensemble of tau at different temperatures by performing all-atom replica-exchange molecular dynamic simulation on K18 monomer with an accumulated simulation time of 26.4 μ*** simulation demonstrates that the compactness,β-structure propensity,and intramolecular interaction of K18 monomer exhibit nonlinear temperature-dependent ***/GNIHHK/337 VEVKSE342 make significant contributions to the temperature dependence of the βpropensity of K18 monomer,while the two fibril-nucleating cores display relatively high β propensity at all *** a specific temperature,K18 monomer adopts the most collapsed state with exposed sites for both persistent and transient *** that more collapsed polypeptide chains were reported to be more prone to phase separate,our results suggest that K18 monomer inherently possesses conformational characteristics favoring *** simulation predicts the importance of DNIKHV/GNIHHK/VEVKSE to the temperature-dependent conformational properties of K18,which is corroborated by CD spectra,turbidity assays,and DIC *** together,we offer a computational and experimental approach to comprehend the structural basis for LLPS by amyloidal building blocks.

关键词： Phase separation tau protein Replica-exchange molecular dynamics

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Military Medical Research 2025年第1期12卷 48-71页

作者： Hui-Yang Lei Gui-Lin Pi Ting He Rui Xiong Jing-Ru Lv Jia-Le Liu Dong-Qin Wu Meng-Zhu Li Kun Shi Shi-Hong Li Na-Na Yu Yang Gao Hui-Ling Yu Lin-Yu Wei Xin Wang Qiu-Zhi Zhou Pei-Lin Zou Jia-Yang Zhou Ying-Zhou Liu Nai-Ting Shen Jie Yang Dan Ke Qun Wang Gong-Ping Liu Xi-Fei Yang Jian-Zhi Wang Ying Yang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Traditional Chinese Medicine the Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Key Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and PreventionShenzhen 518055GuangdongChina Co‑Innovation Center of Neuroregeneration Nantong UniversityNantong 226000JiangsuChina

Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease(AD),which is closely related to tau pathology and hippocampal *** to the heterogeneity of brain neurons,the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain ***,further investigation is ***:We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis,social behavioural tests,hippocampal electrophysiology,immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and ***,we utilized optogenetics and administered ursolic acid(UA)via oral gavage to examine the effects of these agents on social memory in ***:The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1(vCA1)under both physiological conditions and AD-like tau *** tau progressively accumulated,vCA1,especially its excitatory and parvalbumin(PV)neurons,were fully filled with mislocated and phosphorylated tau(p-tau).This finding was not observed for dorsal hippocampal CA1(dCA1).The overexpression of human tau(htau)in excitatory and PV neurons mimicked AD-like tau accumulation,significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within *** excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social ***,1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB(TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social ***:This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau

关键词： Alzheimer’s disease tau protein Ventral hippocampus Social memory Ursolic acid Transcription factor EB(TFEB)

Searching for new drugs to treat Alzheimer’s disease dementia through multiple pathways

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World Journal of Clinical Cases 2025年第1期13卷 22-28页

作者： Hua Bai Xiao-Feng Feng Department of Neurology The Third Affiliated Hospital of Guizhou Medical UniversityDuyun 558099Guizhou ProvinceChina Department of Neurology Wulong Branch of the People's Hospital Affiliated to Chongqing UniversityWulong 408500ChongqingChina Department of Neurology Guizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina

Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic *** treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through *** them,drug therapy to improve cognitive function is *** review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for *** mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.

关键词： Alzheimer's disease Dementia Cholinesterase inhibitor Beta amyloid tau protein

Effects of microtubule-associated protein tau expression on neural stem cell migration after spinal cord injury

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Neural Regeneration Research 2016年第2期11卷 332-337页

作者： Zhi-ping Qi Guo-xiang Wang Peng Xia Ting-ting Hou Hong-li Zhou Tie-jun Wang Xiao-yu Yang Department of Orthopedics the Second Hospital of lilin University Changchun Jilin Province China Department of Orthopedics China-Japan Union Hospital of Jilin University Changchun Jilin Province China

Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau expression in the injured spinal cord. The second aim was to determine whether tau can regulate neural stem cell migration, a critical factor in the successful treatment of spinal cord injury. We established rat models of spinal cord injury and injected them with mouse hippocampal neural stem cells through the tail vein. We used immunohistochemistry to show that the expression of tau protein and the number of migrated neural stem cells were markedly increased in the injured spinal cord. Furthermore, using a Transwell assay, we showed that neural stem cell migration was not affected by an elevated tau concentration in the outer chamber, but it was decreased by changes in intracellular tau phosphorylation state. These results demonstrate that neural stem cells have targeted migration capability at the site of injury, and that although tau is not a chemokine for targeted migration of neural stem cells, intracellular tau phosphorylation/dephosphorylation can inhibit cell migration.

关键词： nerve regeneration spinal cord injury tau protein neural stem cells transwelI chambers phosphatase 2A cell transplantation phosphorylation migration okadaic acid C2-ceramide neural regeneration

Cerebrospinal fluid amyloid beta and tau proteins in atypical Parkinsonism: a review

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Neuroimmunology and Neuroinflammation 2020年第2期7卷 120-131页

作者： Vasilios C.Constantinides George P.Paraskevas Fotini Boufidou Mara Bourbouli Panagiotis G.Paraskevas Leonidas Stefanis Elisabeth Kapaki 1st Department of Neurology National and Kapodistrian University of AthensAthensP.C.11528Greece Department of Neurology University of CreteHeraklion 70013Greece Department of Nursing Technological Educational Institute of CreteHeraklion 71500Greece

Progressive supranuclear palsy,corticobasal degeneration,multiple system atrophy and dementia with Lewy bodies are the most common causes of atypical Parkinsonism and enter the differential diagnosis of Parkinson's *** system atrophy,dementia with Lewy bodies and Parkinson's disease are synucleinopathies,whereas progressive supranuclear palsy and corticobasal degeneration are *** cerebrospinal fluid markers have been applied on cohorts of patients with Parkinsonism,with the aim to develop biomarkers for these *** tau(τΤ),phosphorylated tau at threonine 181(τP-181)and amyloid-beta with 42 amino acids(Aβ42)are considered classical biomarkers for Alzheimer's *** aim of the present study is to review the literature regarding these classical cerebrospinal fluid biomarkers in cohorts with Parkinsonism,as well as present data on novel approaches regarding analysis of these proteins.

关键词： Biomarkers cerebrospinal fluid progressive supranuclear palsy corticobasal degeneration multiple system atrophy dementia with Lewy bodies tau protein phosphorylated tau protein amyloid beta

Bioinspired Self-assembly Nanochaperone Inhibits tau-Derived PHF6 Peptide Aggregation in Alzheimer’s Disease

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Chinese Journal of Polymer Science 2022年第9期40卷 1062-1070页

作者： Lin Zhu Ming-Qing Zhang Hao-Ren Jing Xi-Peng Zhang Lin-Lin Xu Ru-Jiang Ma Fan Huang Lin-Qi Shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationCollege of ChemistryNankai UniversityTianjin 300071China Key Laboratory of Radiopharmacokinetics for Innovative Drugs Chinese Academy of Medical Sciencesand Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300192China Nankai University School ofMedicine Nankai UniversityTianjinChina Department of Colorectal SurgeryTianjin Union Medical CenterTianjin 300074 China Department of Colorectal Surgery Tianjin Union Medical CenterTianjin 300121China

After repeated frustrations with amyloid beta(Aβ)-targeted clinical trials for Alzheimer’s disease(AD)in recent years,the therapeutic focus of AD has gradually shifted from Aβto tau *** misfolding and aggregation of tau protein into neurofibrillary tangles(NFTs)cause neuron death and synaptic dysfunction,and the deposition of NFTs is more closely related to the severity of AD than Aβ***,it has great potential to target tau protein aggregation for AD *** hexapeptide VQIVYK(known as PHF6)in tau protein has been found to play a dominant role for tau aggregation and was widely used as a model to design tau protein aggregation ***,inspired by natural heat shock protein(HSPs),we fabricated a self-assembly nanochaperone based on mixed-shell polymeric micelle(MSPM)as a novel tau-targeted AD *** tunable phase-separated microdomains on the surface,the nanochaperone could effectively bind with PHF6 aggregates,inhibit PHF6 aggregation,block neuronal internalization of PHF6 species,thus significantly alleviating PHF6 mediated ***,the as-prepared nanochaperone could work with proteinase to facilitate the degradation of PHF6 *** bioinspired nanochaperone demonstrated a new way to target tau protein and provided a promising strategy for AD treatment.

关键词： Alzheimer’s disease tau protein PHF6 Nanochaperone Inhibition