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The COVID-19 pandemic and Alzheimer’s disease: mutual risks and mechanisms

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Translational Neurodegeneration 2022年第1期11卷 343-360页

作者： Feng Chen Yanting Chen Yongxiang Wang Qiongwei Ke Lili Cui Guangdong key laboratory of Age-Related Cardiac and Cerebral diseases Department of NeurologyAffiliated Hospital of Guangdong Medical Univer-sityZhanjiangChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of Zoology chinese academy of sciences KunmingYunnanChina.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 is respiratory dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor expressed on cell membranes. Patients with Alzheimer’s disease (AD) are more susceptible to SARS-CoV-2 infection and prone to severe clinical outcomes. Recent studies have revealed some common risk fac-tors for AD and COVID-19. An understanding of the association between COVID-19 and AD and the potential related mechanisms may lead to the development of novel approaches to treating both diseases. In the present review, we first summarize the mechanisms by which SARS-CoV-2 invades the central nervous system (CNS) and then discuss the associations and potential shared key factors between COVID-19 and AD, with a focus on the ACE2 receptor, apolipo-protein E (APOE) genotype, age, and neuroinflammation.

关键词： SARS-CoV-2 COVID-19 Alzheimer’s disease ACE2 APOE Age Neuroinflammation

Why do we study animal toxins?

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Zoological Research 2015年第4期36卷 183-221页

作者： Yun ZHANG key laboratory of animal models and human disease mechanisms of The chinese academy of sciences & yunnan province Kunming Institute of Zoology Chinese Academy of Sciences

Venom （toxins） is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides （TLPs）. We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins.

关键词： Toxins Survival competition Evolution disease mechanism Drug development

Amphibian pore-forming proteinβγ-CAT drives metabolite release from small extracellular vesicles through channel formation

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Zoological Research 2023年第4期44卷 739-742页

作者： Qi-Quan Wang Xin-Qiang Lan Xue-Song Wei Si-Man Xu Ling-Zhen Liu Xian-Ling Bian Lin Zeng Xiao-Long Guo Ying-Qi Guo Wen-Hui Lee Yang Xiang Yun Zhang human Aging Research Institute(HARI)and School of Life Science Nanchang Universityand Jiangxi Key Laboratory of Human AgingNanchangJiangxi 330031China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650201China Center for Excellence in animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650201China Institutional Center for Shared Technologies and Facilities of the Kunming Institute of Zoology Chinese Academy of SciencesKunmingYunnan 650201China

DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and can trigger biological responses at a distance,thus emerging as an additional means of intercellular communication through the release of cellular cargo,such as lipids,nucleic acids,metabolites,and proteins.To date,however,the mechanism by which EV contents are released into extracellular space remains unclear.In our previous study on toads(Bombina maxima),we identified a PFP and trefoil factor complexβγ-CAT(βγ-crystallin fused aerolysin-like protein(α-subunit)and trefoil factor(β-subunit)complex,hence namedβγ-CAT),which assembled under strict regulation in response to environmental cues.Here,we observed that the PFPβγ-CAT colocalized with EVs in the skin of B.maxima in vivo.Using small EVs(sEVs)isolated from B.maxima dermal fibroblast cells and murine fibroblast cells,we found thatβγ-CAT could specifically target and oligomerize on purified EVs,rather than disrupt membrane integrity,and promote the release of different metabolites.Our analysis revealed that a secretory PFP drove metabolite release from EVs through channel formation,providing novel clues for the delivery of EV content into extracellular space.

关键词： release extracellular hence

The 3rd Symposium on animal models of Primates——The Application of Non-human Primates to Basic Research and Translational Medicine

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Journal of Genetics and Genomics 2015年第6期42卷 339-341页

作者： Yong-Gang Yao Yong-Bin Chen Bin Liang key laboratory of animal models and human disease mechanisms of the chinese academy of sciences & yunnan province and Kunming Primate Research CenterKunming Institute of ZoologyChinese Academy of Sciences

In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues：（1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.

关键词： The 3rd Symposium on animal models of Primates The Application of Non-human Primates to Basic Research and Translational Medicine

The role of m6A modification in the biological functions and diseases

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Signal Transduction and Targeted Therapy 2021年第3期6卷 763-778页

作者： Xiulin Jiang Baiyang Liu Zhi Nie Lincan Duan Qiuxia Xiong Zhixian Jin Cuiping Yang Yongbin Chen key laboratory of animal models and human disease mechanisms of chinese academy of sciences&yunnan province Kunming Institute of Zoology650223 KunmingYunnanChina Kunming College of Life Science University of Chinese Academy of Sciences100049 BeijingChina Kunming Medical University 650500 KunmingChina Center for Excellence in animal Evolution and Genetics Chinese Academy of Sciences650223 KunmingYunnanChina

N6-methyladenosine(m6A)is the most prevalent,abundant and conserved internal cotranscriptional modification in eukaryotic RNAs,especially within higher eukaryotic cells.m6A modification is modified by the m6A methyltransferases,or writers,such as METTL3/14/16,RBM15/15B,ZC3H3,VIRMA,CBLL1,WTAP,and KIAA1429,and,removed by the demethylases,or erasers,including FTO and ALKBH5.It is recognized by m6A-binding proteins YTHDF1/2/3,YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1,also known as"readers".Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions,especially in the initiation and progression of different types of human cancers.In this review,we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic,central nervous and reproductive systems.We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation,its regulators and downstream target genes,during cancer progression in above systems.We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

关键词： m6A diseases removed

Avoidance of potentially harmful food cannot be socially transmitted between rats

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Zoological Research 2014年第4期35卷 256-261页

作者： Liang JING Qi-Xin ZHOU Lin XU laboratory of Learning and Memory Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan ProvinceKunming Institute of Zoology University of chinese academy of sciences

The social transmission of food preferences(STFP) is a behavioural task of olfactory memory, in which an observer rat learns safe food odours from a demonstrator rat, and shows preference for this odour in a subsequent choice test. However, previous studies have failed to detect the transmission of information about food of potential danger and food aversion using STFP test. In this study, we tested how demonstrators' health affects the exchange of odour information and whether observers can learn danger information from an unhealthy demonstrator. As expected, the observer rat formed an odour preference after interacting with a demonstrator rat that had just eaten food containing a new odour, however, odour preference rather than aversion was also formed after interacting with a demonstrator rat injected with LiCl(used to induce gastric malaise). Furthermore, anaesthetized demonstrator rats and half-anaesthetized demonstrator rats, which showed obvious motor deficits suggesting an unhealthy state, also socially transmitted food preferences to observers. These results suggest that the social transmission of food preferences task is independent of a demonstrators' health, and that information about dangerous foods cannot be transmitted using this behavioural task.

关键词：食物社会老鼠健康状态传播安全食品相互作用运动障碍

Non-human primate models in drug addiction deserve more attention

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Zoological Research 2014年第3期35卷 172-173页

作者： Jian-Hong WANG key laboratory of animal models and human disease mechanisms of the chinese academy of sciences & yunnan province Kunming Institute of Zoology

Dear Editor, The process of relapse involves firm or aberrant memories of environmental cues associated with drug craving or addiction. To date, it is not known where these memories are stored in the brain, what kinds of regulatory biological factors or molecules are involved, nor why it is so difficult to stop addiction psychologically. Currently, rodent animal models, such as the self-administration and conditioning place preference / aversion paradigm are still widely used in the studies of drug withdrawal syndromes or drug-associate memories. However, the differences between humans and rodents--particularly in terms of genetics, and pathology and pharmacology--have significantly limited the application of further studies on this topic. Essentially, rodents lack the longterm or life-time memories humans possess and lose their drug-associated memory only after a few weeks of withdrawal.

关键词： Non-human primate models in drug addiction deserve more attention PFC

The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models

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Zoological Research 2016年第4期37卷 191-204页

作者： Ming SHAO Tian-Rui XU Ce-Shi CHEN Faculty of Life Science and Technology Kunming University of Science and Technology key laboratory of animal models and human disease mechanisms of the chinese academy of sciences and yunnan province Kunming Institute of Zoology Chinese Academy of Sciences

Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.

关键词： CRISPR/Cas9 animal models Genetherapy

Tree shrew (Tupaia belangeri)as a novel laboratory disease animal model

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Zoological Research 2017年第3期38卷 127-137页

作者： Ji Xiao Rong Liu Ce-Shi Chen Medical Faculty of Kunming University of Science and Technology Kunming Yunnan 650500 China key laboratory of animal models and human disease mechanisms of the chinese academy of sciences and yunnan province Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China

The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.

关键词： Tree shrew （Tupaia belangeri） animal model Transgenic disease