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细胞朊蛋白不影响阿尔茨海默病中十二烷基肌氨酸不溶部分的tau蛋白种子形成和扩散。

The cellular prion protein does not affect tau seeding and spreading of sarkosyl-insoluble fractions from Alzheimer's disease.

作者信息

Sala-Jarque Julia, Gil Vanessa, Andrés-Benito Pol, Martínez-Soria Inés, Picón-Pagès Pol, Hernández Félix, Ávila Jesús, Lanciego José Luis, Nuvolone Mario, Aguzzi Adriano, Gavín Rosalina, Ferrer Isidro, Del Río José Antonio

机构信息

Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri and Reixac 15-21, 08028, Barcelona, Spain.

Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.

出版信息

Sci Rep. 2024 Sep 16;14(1):21622. doi: 10.1038/s41598-024-72232-2.

DOI:10.1038/s41598-024-72232-2
PMID:39284839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11405773/
Abstract

The cellular prion protein (PrP) plays many roles in the developing and adult brain. In addition, PrP binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrP in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer's disease (sAD) into the brain of adult wild-type mice (Prnp), Prnp (ZH3 strain) mice, and mice over-expressing the secreted form of PrP lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrP does not affect tau seeding and spreading in vivo.

摘要

细胞朊蛋白（PrP）在发育中的大脑和成年大脑中发挥着多种作用。此外，PrP以寡聚体和原纤维形式与多种淀粉样蛋白结合，并可能作为异常错误折叠蛋白物种的假定受体。PrP在tau蛋白播种和传播中的作用尚不清楚。在本研究中，我们将特征明确的散发性阿尔茨海默病（sAD）的 Sarkosyl不溶性组分接种到成年野生型小鼠（Prnp）、Prnp（ZH3株）小鼠以及过表达缺乏糖基磷脂酰肌醇（GPI）锚定的分泌型PrP的小鼠（Tg44株）的大脑中。接种后3个月和6个月观察到涉及神经元和少突胶质细胞的磷酸化tau（ptau）播种和传播。通过接种Mapt小鼠并使用特异性抗小鼠和抗人tau抗体发现，宿主tau产生的3Rtau和4Rtau沉积物表明外源性sAD-tau引发了宿主小鼠Mapt基因外显子10剪接的调节。然而，在Prnp基因型之间未观察到tau播种和传播的差异。我们的结果表明，PrP在体内不影响tau播种和传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/20315d73e5fc/41598_2024_72232_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/12a26249397b/41598_2024_72232_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/c3eec54dd8a6/41598_2024_72232_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/3dd6fc60fdf6/41598_2024_72232_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/70001cc0ba54/41598_2024_72232_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/20315d73e5fc/41598_2024_72232_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/12a26249397b/41598_2024_72232_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/c3eec54dd8a6/41598_2024_72232_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/3dd6fc60fdf6/41598_2024_72232_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/70001cc0ba54/41598_2024_72232_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b3/11405773/20315d73e5fc/41598_2024_72232_Fig5_HTML.jpg

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本文引用的文献

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Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-to-Neuron Transmission.淋巴细胞激活基因3促进病理性tau蛋白在神经元间的传递。
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A nonhuman primate model with Alzheimer's disease-like pathology induced by hippocampal overexpression of human tau.
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Alzheimers Res Ther. 2024 Jan 27;16(1):22. doi: 10.1186/s13195-024-01392-0.
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Targeting protein kinases for the treatment of Alzheimer's disease: Recent progress and future perspectives.针对阿尔茨海默病的蛋白激酶治疗靶点：最新进展和未来展望。
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Different tau fibril types reduce prion level in chronically and de novo infected cells.不同的 tau 纤维类型降低慢性和新感染细胞中的朊病毒水平。
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