Neuroscience, Diseases & Related Sciences Symposium

神经科学及其交叉学科前沿系列研讨会

Neurological Diseases, Intermittent fasting and Exosomes

Novermber 19, 2024 | Guangzhou Bio-Island

Center for Medical Research on Innovation & Translation, Guangzhou First People's Hospital, an Affiliated Hospital of South China University of Technology and Guangzhou Medical University

广州市第一人民医院
广州医科大学附属市一人民医院/华南理工大学附属第二医院

主办方：
广州市第一人民医院医学研究与创新转化中心
广州市第一人民医院神经免疫与健康实验室(LNHD.org)
广州市第一人民医院徕卡显微系统共建实验室

协办方：
HONGKONG PLEXON
Leica Microsystem

Syposium overview：The Neuroscience, Diseases & Related Sciences Symposium of Guangzhou First People's Hospital aims to explore global frontiers and research methodologies in both clinical and basic neuroscience as well as related fields. The symposium seeks to promote the development of neuroscience and its interdisciplinary branches.

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○ 9:15-10:15 Intermittent Fasting Alters Chromosome Accessibility, Epigenetic Landscapes, and Gene Expression Dynamics to Shield Against Neurological Diseases
ARUMUGAM, Thiruma Valavan Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, Australia

Abstract: As the brain ages, it undergoes significant cellular changes that indicate compromised bioenergetics, impaired neuroplasticity, disrupted resilience, aberrant neuronal network activity, dysregulated Ca2+ homeostasis, accumulation of oxidatively modified molecules and organelles, and increased inflammation. These alterations make the aging brain vulnerable to neurodegenerative conditions, including Alzheimer’s and Parkinson’s diseases, vascular dementia, and stroke. Recent research has shed light on how sedentary and overindulgent lifestyles accelerate brain aging, while intermittent bioenergetic challenges promote healthier aging. Intermittent fasting (IF), a dietary regimen that alternates between periods of unrestricted food intake and fasting without sacrificing nutritional quality, has been extensively studied in animal models. Prophylactic IF has shown promise in promoting longevity and mitigating the development of age-related dementia. Despite substantial experimental evidence highlighting the benefits of IF against age-related brain diseases, our understanding of the underlying molecular and cellular mechanisms remains limited. Our findings demonstrate that IF induces changes in chromosome accessibility, epigenomic landscape, RNA, and protein profiles. These modifications orchestrate extensive alterations in gene expression compared to ad libitum feeding. Such changes regulate a diverse array of biological processes, providing plausible explanations for the beneficial effects of IF. This discovery may pave the way for a paradigm shift in using IF as a universally accessible, drug-free preventive lifestyle management strategy, leveraging its epigenetic modifications for a range of positive health outcomes.

BIO: Professor Arumugam obtained his Bachelor’s Degree in Medical Science with Honors from the University of Sydney in 1998 and a Doctor of Philosophy in Pharmacology from the University of Queensland in 2003. He completed post-doctoral training at Louisiana State University Health Sciences Center in Shreveport, USA, under Professor Neil Granger, and at the National Institute of Health, Baltimore, USA, under Professor Mark Mattson. Establishing his independent laboratory at Texas Tech University Health Sciences Center in 2007, he later transitioned to The University of Queensland (UQ) as a Senior Lecturer, focusing on CNS neurodegeneration and ischemic stroke. In 2011, he was honored with the UQ Foundation Research Excellence Award and an Australian Research Council (ARC) Future Fellowship. He was appointed Associate Professor at the National University of Singapore in 2013 and subsequently joined La Trobe University in March 2020. Professor Arumugam’s research is primarily dedicated to unraveling neuronal cell death mechanisms in stroke and vascular dementia, with an emphasis on identifying novel therapeutic targets. Furthermore, his investigations extend to exploring the impact of intermittent metabolic switching on brain aging and related diseases. His contributions have appeared in journals such as Nature Medicine, Nature Neuroscience, Circulation, PNAS, Molecular Psychiatry, Theranostics, Cell Metabolism, and Nature Communications. With over 195 articles and three book chapters, his work has garnered over 23,000 citations (Google Scholar) and he maintains an h-index of 79.

○ 10:15-11:15 Exosomes for epigenome editing in Alzheimer’s disease
JO, Dong-Gyu School of Pharmacy, Sungkyunkwan University, Seoul, Korea

Abstract: Effective intracellular delivery of therapeutic proteins can potentially treat a wide array of diseases. However, efficient delivery of functional proteins across the cell membrane remains challenging. Exosomes are nanosized vesicles naturally secreted by various types of cells and may serve as promising nanocarriers for therapeutic biomolecules. Here, we engineered exosomes equipped with a photoinducible cargo protein release system, termed mMaple3-mediated protein loading into and release from exosome (MAPLEX), in which cargo proteins can be loaded into the exosomes by fusing them with photocleavable protein (mMaple3)–conjugated exosomal membrane markers and subsequently released from the exosomal membrane by inducing photocleavage with blue light illumination. Using this system, we first induced transcriptional regulation by delivering octamer-binding transcription factor 4 and SRY-box transcription factor 2 to fibroblasts in vitro. Second, we induced in vivo gene recombination in Cre reporter mice by delivering Cre recombinase. Last, we achieved targeted epigenome editing in the brains of 5xFAD and 3xTg-AD mice, two models of Alzheimer’s disease. Administration of MAPLEXs loaded with β-site amyloid precursor protein cleaving enzyme 1 (Bace1)–targeting single guide RNA–incorporated dCas9 ribonucleoprotein complexes, coupled with the catalytic domain of DNA methyltransferase 3A, resulted in successful methylation of the targeted CpG sites within the Bace1 promoter. This approach led to a significant reduction in Bace1 expression, improved recognition memory impairment, and reduced amyloid pathology in 5xFAD and 3xTg-AD mice. These results suggest that MAPLEX is an efficient intracellular protein delivery system that can deliver diverse therapeutic proteins for multiple diseases.

BIO: Dong-Gyu Jo is a Professor of the School of Pharmacy at Sungkyunkwan University. He received his Ph.D. in Molecular Neurobiology from the Gwangju Institute of Science & Technology in 2002. From 2003 to 2007, he worked in the Laboratory of Neurosciences at the National Institute on Aging, National Institutes of Health in the USA as a Postdoctoral fellow. Then in 2007, as an independent principal investigator, he started his own laboratory at Sungkyunkwan University in Korea. His laboratory employs a multifaceted array of experimental models of aging and age-related neurodegenerative disorders in order to establish the cellular and biochemical changes that occur during aging and in disorders such as Alzheimer's, Parkinson's, and stroke. In addition to identifying the molecular and cellular alterations that lead to neuronal degeneration in age-related neurological diseases, his group is elucidating the cellular and biochemical signaling mechanisms that allow successful brain aging. They are also running drug discovery projects spanning the range from target validation and initial high-throughput screening to lead identification to advance the discovery of new, efficacious therapies for the treatment, delay of progression, or prevention of Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, age-related cognitive decline, and stroke. Recently, the research interests of his group have been expanded to the field of extracellular vesicles.

○ 11:15-12:15 Translational Research in Dementia: An Omics Approach and a Proposal to Link Intermittent Fasting with Cognitive Resilience
LAI, Mitchell K.P. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore

Abstract: Alzheimer’s disease (AD) and vascular dementia (VaD) remain two of the commonest causes of dementia in the elderly, and represent unmet needs in terms of efficient, early diagnosis, disease-modifying treatments, and prevention. Adding to the clinical complexity is the frequent coexistence of both amyloid and cerebrovascular pathologies, especially in Asian cohorts. In this talk, I showcase my lab’s efforts in characterizing AD and VaD using proteomic and lipidomic approaches. I also introduce the concept of cognitive resilience (CR) in the context of cognitive decline and dementia, as well as how knowledge gained from intermittent fasting studies may inform identification and amplification of CR targets as a potential strategy to preserve cognitive function or even reverse the dementia process.

BIO: LAI, Kim Peng Mitchell (赖君鹏) obtained his BSc in Biological Sciences from the University of Alberta, Canada; and PhD in Medicine from the University of Sydney, Australia. Thereafter he was Principal Research Scientist at the Department of Clinical Research, Singapore General Hospital and Visiting Senior Fellow at the Wolfson Centre for Age-Related Diseases, King’s College London, before moving to the Yong Loo Lin School of Medicine, National University of Singapore, where he is now Senior Lecturer and Education Director with the Department of Pharmacology, as well as Principal Investigator with the Memory, Ageing and Cognition Centre. His biomedical research interest is in dementia, specifically in the areas of identification of novel drug targets and biomarkers for Alzheimer’s disease and vascular dementia. He has authored over 100 research articles and several book chapters. In his role as a medical educator, he is involved in teaching and curriculum development of pharmacology courses for life science, nursing, dental and medical students. He is also Director of the Youth Programme in Pharmacological and Biomedical Sciences, where he oversees the Department’s outreach efforts and vacation courses for international students.

○ 12:15-12:30 The journal - Aging Reserch - SciOpen
CHEN, Guobin School of Medicine, Jinan University

Abstract: Aging Research is an Open Access publication addressing the biology and medicine issues of aging and aging-related diseases.
Aging Research publishes original research results that are of unusual significance or broad conceptual or technical advances in all areas of aging, longevity and aging related health issues. The journal focuses on the following research: to explore the process, mechanism, biomarkers, anti-aging strategies or drugs at the population, individual, system, organ, tissue, cell and subcellular levels; to study the epidemiological characteristics, pathogenesis, pathophysiological processes, diagnostic criteria, clinical experiments and translational research of age-related diseases.

BIO: Guobing Chen is Professor of Immunology, Director of Institute of Geriatric Immunology and Dean of the School of Medicine, Jinan University in China. His group is working on how the immune system changes during aging, to identify the biomarkers of immune aging, explore the immunological factors relevant to geriatric diseases, such as infectious, autoimmune and neurodegenerative diseases, finally to develop the efficient treatment to prevent aging and aging related diseases.

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主办方：
广州市第一人民医院神经免疫与健康实验室(LNHD.org)
广州市第一人民医院徕卡显微系统共建实验室
广州市第一人民医院（广州医科大学附属市一人民医院/华南理工大学附属第二医院） 医学研究与创新转化中心

协办方：

地址：生物岛寰宇二路10号B栋9楼

交通指引：【会场定位】导航至“生物岛寰宇二路10号B栋”，从B栋一楼大门进入。

自驾指引：【停车场入口定位】导航至“广州国际生物岛园区-南区”前行5米右转进停车场负一楼，下坡后左转后右转，直行到底进入B区后停车，B栋电梯厅在前行方向左前方。