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新型云母纳米颗粒STB-MP对阿尔茨海默病患者诱导的PSC来源的皮质脑类器官模型的影响。

The Effect of a Novel Mica Nanoparticle, STB-MP, on an Alzheimer's Disease Patient-Induced PSC-Derived Cortical Brain Organoid Model.

作者信息

Kim Nam Gyo, Jung Dong Ju, Jung Yeon-Kwon, Kang Kyung-Sun

机构信息

Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.

Sol to B Co., Ltd., Gangnam-gu, Seoul 06242, Republic of Korea.

出版信息

Nanomaterials (Basel). 2023 Feb 27;13(5):893. doi: 10.3390/nano13050893.

DOI:10.3390/nano13050893
PMID:36903771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10005775/
Abstract

Alzheimer's disease (AD) is one of the most well-known neurodegenerative diseases, with a substantial amount of advancements in the field of neuroscience and AD. Despite such progress, there has been no significant improvement in AD treatments. To improve in developing a research platform for AD treatment, AD patient-derived induced pluripotent stem cell (iPSC) was employed to generate cortical brain organoids, expressing AD phenotypes, with the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau (pTau). We have investigated the use of a medical grade mica nanoparticle, STB-MP, as a treatment to decrease the expression of AD's major hallmarks. STB-MP treatment did not inhibit the expression of pTau; however, accumulated Aβ plaques were diminished in STB-MP treated AD organoids. STB-MP seemed to activate the autophagy pathway, by mTOR inhibition, and also decreased γ-secretase activity by decreasing pro-inflammatory cytokine levels. To sum up, the development of AD brain organoids successfully mimics AD phenotype expressions, and thus it could be used as a screening platform for novel AD treatment assessments.

摘要

阿尔茨海默病（AD）是最广为人知的神经退行性疾病之一，神经科学和AD领域取得了大量进展。尽管有这些进展，但AD治疗并未取得显著改善。为了改进AD治疗研究平台的开发，利用源自AD患者的诱导多能干细胞（iPSC）生成表达AD表型的皮质脑类器官，伴有淀粉样β蛋白（Aβ）和过度磷酸化tau蛋白（pTau）的积累。我们研究了使用医用级云母纳米颗粒STB-MP作为一种治疗方法来降低AD主要特征的表达。STB-MP治疗并未抑制pTau的表达；然而，在经STB-MP处理的AD类器官中，积累的Aβ斑块减少。STB-MP似乎通过抑制mTOR激活自噬途径，还通过降低促炎细胞因子水平降低γ-分泌酶活性。总之，AD脑类器官的开发成功模拟了AD表型表达，因此可作为新型AD治疗评估的筛选平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/bec07b4e527c/nanomaterials-13-00893-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/54a6ea5bb196/nanomaterials-13-00893-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/284104bc29f9/nanomaterials-13-00893-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/699736ae7c95/nanomaterials-13-00893-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/edbcb32f43a0/nanomaterials-13-00893-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/88679492b4c2/nanomaterials-13-00893-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/bec07b4e527c/nanomaterials-13-00893-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/54a6ea5bb196/nanomaterials-13-00893-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/284104bc29f9/nanomaterials-13-00893-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/699736ae7c95/nanomaterials-13-00893-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/edbcb32f43a0/nanomaterials-13-00893-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/88679492b4c2/nanomaterials-13-00893-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/10005775/bec07b4e527c/nanomaterials-13-00893-g004.jpg

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