机构：[1]Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany[2]VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, O&N IV Herestraat 49—box 602, 3000 Leuven, Belgium[3]Medical Faculty, Core Facility Transgenic Animal and Genetic Engineering Models (TRAM), University of Münster, Von-Esmarch-Str. 56, D-48149 Münster, Germany[4]Institute of Experimental Pathology, Centre for Molecular Biology of Inflammation (ZMBE), University of Münster, Von-Esmarch-Str. 56, D-48149 Münster, Germany[5]Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation (ZMBE), University of Münster, Von-Esmarch-Strasse 56, D-48149 Münster, Germany[6]Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610212, China四川大学华西医院
Alzheimer's disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (Aβ) play a crucial role in the pathology of AD. In familial AD, Aβ are generated from the full-length amyloid beta precursor protein (APP) via dysregulated proteolytic processing; however, in the case of sporadic AD, the mechanism of Aβ biogenesis remains elusive. circRNAs are a class of transcripts preferentially expressed in brain. We identified a circRNA harboring the Aβ-coding region of the APP gene termed circAβ-a. This circular RNA was detected in the brains of AD patients and non-dementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circAβ-a is efficiently translated into a novel Aβ-containing Aβ175 polypeptide (19.2 KDa) in both cultured cells and human brain. Furthermore, Aβ175 was shown to be processed into Aβ peptides-a hallmark of AD. In summary, our analysis revealed an alternative pathway of Aβ biogenesis. Consequently, circAβ-a and its corresponding translation product could potentially represent novel therapeutic targets for AD treatment. Importantly, our data point to yet another evolutionary route for potentially increasing proteome complexity by generating additional polypeptide variants using back-splicing of primary transcripts that yield circular RNA templates.
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外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|3 区生物学
小类|4 区细胞生物学
最新[2025]版：
大类|2 区生物学
小类|3 区细胞生物学
第一作者：
第一作者机构：[1]Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany[2]VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, O&N IV Herestraat 49—box 602, 3000 Leuven, Belgium[3]Medical Faculty, Core Facility Transgenic Animal and Genetic Engineering Models (TRAM), University of Münster, Von-Esmarch-Str. 56, D-48149 Münster, Germany
通讯作者：
通讯机构：[1]Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany[2]VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, O&N IV Herestraat 49—box 602, 3000 Leuven, Belgium[3]Medical Faculty, Core Facility Transgenic Animal and Genetic Engineering Models (TRAM), University of Münster, Von-Esmarch-Str. 56, D-48149 Münster, Germany
推荐引用方式(GB/T 7714)：
Mo Dingding,Li Xinping,Raabe Carsten A,et al.Circular RNA Encoded Amyloid Beta peptides-A Novel Putative Player in Alzheimer's Disease.[J].Cells.2020,9(10):doi:10.3390/cells9102196.
APA：
Mo Dingding,Li Xinping,Raabe Carsten A,Rozhdestvensky Timofey S,Skryabin Boris V&Brosius Juergen.(2020).Circular RNA Encoded Amyloid Beta peptides-A Novel Putative Player in Alzheimer's Disease..Cells,9,(10)
MLA：
Mo Dingding,et al."Circular RNA Encoded Amyloid Beta peptides-A Novel Putative Player in Alzheimer's Disease.".Cells 9..10(2020)
