出版者・発行元：Cold Spring Harbor Laboratory  

Abstract

Although the amyloid beta (Aβ) hypothesis¹has long been central to Alzheimer’s disease (AD) research, effective therapeutic strategies remain elusive^2,3. Here we re-evaluate the functions of amyloid precursor protein (APP) and reveal its critical function in protecting against nuclear impairment-induced cell death and inflammation^4,5. Overexpression of APP mitigated etoposide or lamin A knockdown-induced nuclear damage, while APP removal or mutations exacerbated these effects. Interestingly, neurons differentiated from induced pluripotent stem cells (iPSCs) exhibited similar patterns, and notably, familial AD-associated mutant APP failed to confer protection against nuclear impairment. We identify APP’s interaction with a cytoplasmic structure of nuclear origin, termed “nuclear waste”, and propose its role in extracellular waste disposal. Intriguingly, cells lacking APP showed impaired nuclear waste clearance, leading to abnormal cytoplasmic accumulation of the nuclear waste. Similarly, neuron-specific APP overexpression using adeno-associated virus (AAV) in mice reduced neuronal death and inflammation caused by nuclear damage. Conversely, shRNA-mediated APP exacerbated these effects, and mutant APP associated with familial AD lacked protective effects. Moreover, postmortem analysis of AD brains revealed accumulation of abnormal nuclear waste in the neurocytoplasm, irregular nuclear morphology, and reduced APP levels per neuron. Our data underscore APP’s crucial role in disposing of nuclear waste, maintaining cellular homeostasis, and suggest its dysregulation as a potential contributor to AD pathogenesis. Restoring APP waste clearance in AD could be a promising target for disease-modifying therapies.

DOI： 10.1101/2024.02.10.579739

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media {LLC}  

<jats:title>Abstract</jats:title><jats:p>Traditional medicine (TM) is a significant resource for primary healthcare management all over the world, and principally in Africa. Quality improvement activities that promote evidence-based practices and the integration of traditional medicine into primary healthcare systems can help improve the quality of patient care. In the Republic of Benin (West Africa), traditional medicine practitioners (TMPs) provide different treatments and ways of use, depending on the ailments and the medicinal plants used. The present study aimed at documenting the knowledge, attitudes and practices of Beninese TMPs regarding the use of medicinal plants and the challenges associated with their activities. A focus group survey was conducted using semi-structured interviews with a sample of 91 TMPs in 8 departments of the Republic of Benin. The respondents had an average age of 50 years old and belonged to various categories of TMPs. Medicinal plants are harvested depending on the season and time of the day, and are dried in the shade before being used as decoctions or infusions. Nevertheless, the majority of TMPs do not conduct the necessary tests for quality control, efficacy or toxicity of the proposed remedies, which raises several scientific interrogations, particularly for the treatment of mental and brain-related disorders. Among ~ 110 plants used in the treatment of several pathologies, 66 were revealed as threatened species. The challenges faced by TMPs are mainly material, financial and technical difficulties. The present study reports the importance of intervention to modernize TM practices in Benin. Quality improvement could enhance healthcare delivery and provide support for evidence-based interventions aimed at addressing behavioral, social, and environmental determinants of health.</jats:p>

DOI： 10.1038/s41598-023-46647-2

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two debilitating neurodevelopmental disorders. The former is associated with social impairments whereas the latter is associated with inattentiveness, hyperactivity, and impulsivity. There is recent evidence that both disorders are somehow related and that genes may play a large role in these disorders. Despite mounting human and animal research, the neurological pathways underlying ASD and ADHD are still not well understood. Scientists investigate neurodevelopmental disorders by using animal models that have high similarities in genetics and behaviours with humans. Mice have been utilized in neuroscience research as an excellent animal model for a long time; however, the zebrafish has attracted much attention recently, with an increasingly large number of studies using this model. In this review, we first discuss ASD and ADHD aetiology from a general point of view to their characteristics and treatments. We also compare mice and zebrafish for their similarities and discuss their advantages and limitations in neuroscience. Finally, we summarize the most recent and existing research on zebrafish and mouse models of ASD and ADHD. We believe that this review will serve as a unique document providing interesting information to date about these models, thus facilitating research on ASD and ADHD.

DOI： 10.3390/ijms23147550

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Georg Thieme Verlag {KG}  

DOI： 10.1055/a-1770-7581

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11418-021-01579-x

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会議種別：ポスター発表  

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：ポスター発表  

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会議種別：ポスター発表  

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記述言語：日本語   会議種別：口頭発表（一般）  

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