HHV-6A infection dysregulates autophagy/UPR interplay increasing beta amyloid production and tau phosphorylation in astrocytoma cells as well as in primary neurons, possible molecular mechanisms linking viral infection to Alzheimer's disease

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Article

Romeo, Maria Anele¹  Gilardini Montani, Maria Saveria¹  Gaeta, Aurelia²  D'Orazi, Gabriella^3,4  Faggioni, Alberto¹  Cirone, Mara¹ 

[1] Sapienza Univ Rome, Dept Expt Med, Fdn Cenci Bolognetti, Lab Inst Pasteur Italia, Rome, Italy

[2] Sapienza Univ Rome, Dept Mol Med, Rome, Italy

[3] Regina Elena Inst Canc Res, Dept Res Adv Diagnost & Technol Innovat, Rome, Italy

[4] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, I-66100 Chieti, Italy

关键词: Alzheimer's disease;    HHV-6A;    Neurons;    Autophagy/UPR;    A beta;    Tau phosphorylation;   

DOI  :  10.1016/j.bbadis.2019.165647

来源: Elsevier

【 摘 要 】

HHV-6A and HHV-6B are neurotropic viruses able to dysregulate autophagy and activate ER stress/UPR in several cell types. The appropriate functioning of these processes is required for cell homeostasis, particularly in post-mitotic cells such as neuronal cells. Interestingly, neurodegenerative diseases such as Alzheimer's disease (AD) are often accompanied by autophagy dysregulation and abnormal UPR activation. This study demonstrated for the first time that HHV-6A infection of astrocytoma cells and primary neurons reduces autophagy, increases AD production and activates ER stress/UPR promoting tau protein hyper-phosphorylation. Our results support previous studies suggesting that HHV-6A infection may play a role in AD and unveil the possible underlying molecular mechanisms involved.

【 授权许可】

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