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Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

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Hyperdense basilar artery sign as a reliable predictor of acute basilar artery occlusion: Case report and literature review

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Visual Journal of Emergency Medicine 2025年 38卷 102179-102179页

作者： Wu, Xiaoxin Sheng, Wenli Ye, Fei Department of Neurology The First Affiliated Hospital Sun Yat-sen University Guangzhou China Neuroscience and Behavioral Disorders Program Duke-NUS Medical School National University of Singapore Singapore Singapore

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Glucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability

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Life Metabolism 2025年第1期4卷 17-34页

作者： Yik-Lam Cho Hayden Weng Siong Tan Jicheng Yang Basil Zheng Mian Kuah Nicole Si Ying Lim Naiyang Fu Boon-Huat Bay Shuo-Chien Ling Han-Ming Shen Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Department of Anatomy Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117594Singapore Cancer and Stem Cell Biology Program Duke-NUS Medical SchoolSingapore 169857Singapore NUS Centre for Cancer Research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Programs in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore 169857Singapore Healthy Longevity Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Faculty of Health Sciences MOE Frontier Centre for Precision OncologyUniversity of MacaoMacao 999078China

Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the pentose phosphate pathway(PPP)in *** metabolism is closely implicated in the regulation of mitophagy,a selective form of autophagy for the degradation of damaged *** PPP and its key enzymes such as G6PD possess important metabolic functions,including biosynthesis and maintenance of intracellular redox balance,while their implication in mitophagy is largely ***,via a whole-genome CRISPR-Cas9 screening,we identified that G6PD regulates PINK1(phosphatase and tensin homolog[PTEN]-induced kinase 1)-Parkinmediated *** function of G6PD in mitophagy was verified via multiple approaches.G6PD deletion significantly inhibited mitophagy,which can be rescued by G6PD ***,while the catalytic activity of G6PD is required,the known PPP functions per se are not involved in mitophagy ***,we found a portion of G6PD localized at mitochondria where it interacts with PINK1.G6PD deletion resulted in an impairment in PINK1 stabilization and subsequent inhibition of ubiquitin phosphorylation,a key starting point of ***,we found that G6PD deletion resulted in lower cell viability upon mitochondrial depolarization,indicating the physiological function of G6PD-mediated mitophagy in response to mitochondrial *** summary,our study reveals a novel role of G6PD as a key positive regulator in mitophagy,which bridges several important cellular processes,namely glucose metabolism,redox homeostasis,and mitochondrial quality control.

关键词： G6PD mitophagy PINK1 ROS NADPH PPP

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Cell replacement for Parkinson's disease:advances and challenges

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Neural Regeneration Research 2023年第12期18卷 2693-2694页

作者： Bin Xiao Eng-King Tan Department of Neurology National Neuroscience InstituteSingapore Neuroscience and Behavioral Disorders Program Duke-NUS Medical SchoolSingapore

Parkinson's disease(PD), characterized by the loss of dopaminergic(DA) neurons in the substantia nigra pars compacta(SNpc) of the midbrain, is a prototype neurological disease that is suitable for cellular replacement therapy. Levodopa has been utilized to replace the insufficient dopamine released by degenerating DA neurons since the 1960s and it remains the cornerstone of PD treatment. However, as the disease progresses.

关键词： dopamine corners replace

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Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: Promises and challenges

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Pharmacological Research 2025年 216卷 107770页

作者： Zhou, Zhi Dong Yi, Lingxiao Popławska-Domaszewicz, Karolina Chaudhuri, Kallol Ray Jankovic, Joseph Tan, Eng King National Neuroscience Institute of Singapore 11 Jalan Tan Tock Seng 308433 Singapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical School 8 College Road 169857 Singapore Department of Neurology Poznan University of Medical Sciences Poznan 60-355 Poland Parkinson's Foundation Centre of Excellence King's College Hospital Denmark Hill London SE5 9RS United Kingdom Department of Basic and Clinical Neuroscience The Maurice Wohl Clinical Neuroscience Institute King's College London Cutcombe Road London SE5 9RT United Kingdom Parkinson's Disease Center and Movement Disorders Clinic Department of Neurology Baylor College of Medicine Houston TX United States

Glucagon-like peptide-1 (GLP-1) receptor agonists (GRA) belong to a class of compounds that reduce blood glucose and energy intake by simulating actions of endogenous incretin hormone GLP-1 after it is released by the gut following food consumption. They are used to treat type 2 diabetes mellitus (T2DM) and obesity and have systemic effects on various organs, including the brain, liver, pancreas, heart, and the gut. Patients with T2DM have a higher risk of developing neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), accompanied by more severe motor deficits and faster disease progression, suggesting dysregulation of insulin signaling in these diseases. Experimental studies have shown that GRA have protective effects to modulate neuroinflammation, oxidative stress, mitochondrial and autophagic functions, and protein misfolding. Hence the compounds have generated enormous interest as novel therapeutic agents against NDs. To date, clinical trials have shown that three GRA, exenatide, liraglutide and lixisenatide can improve motor deficits as an add-on therapy in PD patients and liraglutide can improve cognitive function in AD patients. The neuroprotective effects of these and other GRA, such as PT320 (a sustained-released exenatide) and semaglutide, are still under investigation. The dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonists have been demonstrated to have beneficial effects in AD and PD mice models. Overall, GRA are highly promising novel drugs, but future clinical studies should identify which subsets of patients should be targeted as potential candidates for their symptomatic and/or neuroprotective benefits, investigate whether combinations with other classes of drugs can further augment their efficacy, and evaluate their long-term disease-modifying and adverse effects. © 2025 The Authors

关键词： Alzheimer's disease GLP-1 receptor agonists Glucagon-like peptide-1 Neurodegenerative diseases Parkinsons' disease Type 2 diabetes mellitus

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Sociodemographic influences on substance use in psychosis in an African cohort

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Schizophrenia Research 2025年 281卷 157-163页

作者： Campbell, Megan L. Odokonyero, Raymond Akena, Dickens Alemayehu, Melkam Atwoli, Lukoye Chibnik, Lori B. Gelaye, Bizu Gichuru, Stella Kariuki, Symon M. Koenen, Karestan C. Kwobah, Edith Kyebuzibwa, Joseph Mwema, Rehema M. Newton, Charles R.J.C. Post, Kristianna Pretorius, Adele Stevenson, Anne Stroud, Rocky E. Teferra, Solomon Zingela, Zukiswa Stein, Dan J. Hook, Kimberly Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER) Program Harvard T.H. Chan School of Public Health and the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT United States SAMRC Unit on Risk & Resilience in Mental Disorders Department of Psychiatry Neuroscience Institute University of Cape Town South Africa Department of Psychiatry School of Medicine College of Health Sciences Makerere University Uganda Department of Psychiatry School of Medicine College of Health Sciences Addis Ababa University Ethiopia Neuroscience Unit KEMRI-Wellcome Trust Research Program Kenya Stanley Center for Psychiatric Research Broad Institute of Harvard and MIT United States Department of Epidemiology Harvard T. H. Chan School of Public Health United States Department of Neurology Massachusetts General Hospital Harvard Medical School United States Department of Psychiatry Massachusetts General Hospital Harvard Medical School United States Department of Social and Behavioral Sciences Harvard T.H. Chan School of Public Health United States Department of Mental Health Moi Teaching and Referral Hospital Eldoret Kenya Department of Psychiatry University of Oxford United Kingdom Department of Psychiatry Faculty of Medicine and Health Sciences Stellenbosch University South Africa Executive Dean's Office Faculty of Health Sciences Nelson Mandela University South Africa

Background: Substance use is common among individuals with psychotic disorders, but limited research exists on the variations in substance use across countries in Africa. This study aims to investigate the frequency of alcohol, tobacco, cannabis, and khat consumption in individuals with bipolar disorder (BD) and schizophrenia (SCZ) across four African countries: South Africa, Ethiopia, Kenya, and Uganda. Methods: We utilized data from the Neuropsychiatric Genetics of African Populations-Psychosis project, a large case-control study which will soon have genetic data on over 42,000 participants, half with psychosis. Information on substance use was collected using the Alcohol, Smoking and Substance Involvement Screening Test v3 (ASSIST). The outcome was categorized into never (lifetime usage, no), irregular usage (weekly or monthly) and regular (daily use) based on reported frequency in the past three months. Each substance was modeled individually as an outcome in ordinal regression model adjusting for demographic factors of sex, education and country. Stratified analyses were performed to assess country-specific effects. Results: Individuals with BD had significantly higher odds of alcohol consumption compared to those with SCZ. Males showed higher odds of alcohol, tobacco, and khat consumption compared to females. Significant variations in alcohol, tobacco, and cannabis consumption were observed across different study countries. Education level was significantly associated with khat consumption, with higher education levels associated with lower odds of consumption. Conclusion: Country and sex-specific differences in substance use behaviors exist in a large-scale African case-control study of people with psychosis. The findings here are in line with previous work regarding sex and regional differences, though they differ from studies conducted in US populations in that minimal evidence was found to support a relationship between level of education and frequency of

关键词： African cohort Bipolar disorder Psychosis Schizophrenia Substance use

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The role of sleep duration and sleep disordered breathing in gestational diabetes mellitus

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Neurobiology of Sleep and Circadian Rhythms 2018年 4卷 34-43页

作者： Gooley, Joshua J. Mohapatra, Litali Twan, Derek Chao Kuan Center for Cognitive Neuroscience Program in Neuroscience and Behavioral Disorders Duke-NUS Medical School 8 College Road Singapore 169857 Singapore

Many women experience sleep problems during pregnancy. This includes difficulty initiating and maintaining sleep due to physiologic changes that occur as pregnancy progresses, as well as increased symptoms of sleep-disordered breathing (SDB). Growing evidence indicates that sleep deficiency alters glucose metabolism and increases risk of diabetes. Poor sleep may exacerbate the progressive increase in insulin resistance that normally occurs during pregnancy, thus contributing to the development of maternal hyperglycemia. Here, we critically review evidence that exposure to short sleep duration or SDB during pregnancy is associated with gestational diabetes mellitus (GDM). Several studies have found that the frequency of GDM is higher in women exposed to short sleep compared with longer sleep durations. Despite mixed evidence regarding whether symptoms of SDB (e.g., frequent snoring) are associated with GDM after adjusting for BMI or obesity, it has been shown that clinically-diagnosed SDB is prospectively associated with GDM. There are multiple mechanisms that may link sleep deprivation and SDB with insulin resistance, including increased levels of oxidative stress, inflammation, sympathetic activity, and cortisol. Despite emerging evidence that sleep deficiency and SDB are associated with increased risk of GDM, it has yet to be demonstrated that improving sleep in pregnant women (e.g., by extending sleep duration or treating SDB) protects against the development of hyperglycemia. If a causal relationship can be established, behavioral therapies for improving sleep can potentially be used to reduce the risk and burden of GDM. © 2017 The Authors

关键词： Gestational diabetes Metabolism Pregnancy Sleep disordered breathing Sleep duration Women

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Mitochondrial homeostasis in Parkinson＇s disease-a triumvirate rule？

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Neural Regeneration Research 2017年第8期12卷 1270-1272页

作者： Chee-Hoe Ng Liting Hang Kah-Leong Lim National Neuroscience Institute Singapore Neuroscience & Behavioral Disorders Program Duke-NUSMedical School Singapore Department of Physiology National University of SingaporeSingapore NUS Graduate School for Integrative Sciences and Engineering Singapore

Mitochondrial dysfunction in Parkinson＇s disease：Mitochondria are the primary energy generator of the cell and they are important for cell survival and *** mitochondrial homeostasis is frequently reported in human d... 详细信息

关键词： PPAR PD cell PGC AMPK Mitochondrial homeostasis in Parkinson’s disease-a triumvirate rule

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Diurnal Regulation of Lipid Metabolism and Applications of Circadian Lipidomics

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Journal of Genetics and Genomics 2014年第5期41卷 231-250页

作者： Joshua J.Gooley Eric Chern-Pin Chua Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical SchoolSingapore Division of Sleep and Circadian Disorders Departments of Medicine and Neurology Brigham and Women's Hospital Division of Sleep Medicine Harvard Medical School Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore

The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.

关键词： Circadian Metabolism Lipids Lipidomics Metabolomics Chronobiology

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Classification of musical styles using liquid state machines

Classification of musical styles using liquid state machines

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2010 6th IEEE World Congress on Computational Intelligence, WCCI 2010 - 2010 International Joint Conference on Neural Networks, IJCNN 2010

作者： Ju, Han Xu, Jian-Xin Vandongen, Antonius M.J. Program for Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore Singapore Department of Electrical and Computer Engineering National University of Singapore Singapore

ISBN: (纸本)9781424469178

Music Information Retrieval (MIR) is an interdisciplinary field that facilitates indexing and content-based organization of music databases. Music classification and clustering is one of the major topics in MIR. Music can be defined as 'organized sound'. The highly ordered temporal structure of music suggests it should be amendable to analysis by a novel spiking neural network paradigm: the liquid state machine (LSM). Unlike conventional statistical approaches that require the presence of static input data, the LSM has a unique ability to classify music in real-time, due to its dynamics and fading-memory. This paper investigates the performance of an LSM in classifying musical styles (ragtime vs. classical), as well as its ability to distinguish music from note sequences without temporal structure. The results show that the LSM performs admirably in this task. © 2010 IEEE.

关键词： Music

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