Angiogenin and tRNA fragments in Parkinson's disease and neurodegeneration

Acta Pharmacologica Sinica
Jochen H M Prehn, Elisabeth Jirström

Abstract

In this review, we summarise the evidence for a role of the ribonuclease angiogenin in the pathophysiology of neurodegenerative disorders, with a specific focus on Parkinson's disease (PD). Angiogenin is a stress-induced, secreted ribonuclease with both nuclear and cytosolic activities. Loss-of-function mutations in the angiogenin gene (ANG) have been initially discovered in familial cases of amyotrophic lateral sclerosis (ALS), however, variants in ANG have subsequently been identified in PD and Alzheimer's disease. Delivery of angiogenin protein reduces neurodegeneration and delays disease progression in in vitro and in vivo models of ALS and in vitro models of PD. In the nucleus, angiogenin promotes ribosomal RNA transcription. Under stress conditions, angiogenin also translocates to the cytosol where it cleaves non-coding RNA into RNA fragments, in particular transfer RNAs (tRNAs). Stress-induced tRNA fragments have been proposed to have multiple cellular functions, including inhibition of ribosome biogenesis, inhibition of protein translation and inhibition of apoptosis. We will discuss recent evidence of tRNA fragment accumulation in PD, as well as their potential neuroprotective activities.

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Citations

Sep 6, 2020·Nucleic Acids Research·Rogan Magee, Isidore Rigoutsos
Mar 24, 2020·Acta Pharmacologica Sinica·Xue-Chu Zhen, Hong-Yuan Chu
Sep 6, 2020·Journal of Hematology & Oncology·Mengqian YuYan Lu
Feb 3, 2021·International Journal of Molecular Sciences·Mayuresh Anant Sarangdhar, Ramanjaneyulu Allam
Mar 9, 2021·Clinical, Cosmetic and Investigational Dermatology·Natalia V YurinaAlexey V Purtov
May 18, 2021·BioMed Research International·Amir Hossein AalamiAmirhossein Sahebkar
Aug 4, 2021·Aging and Disease·Ya YuanDeying Yang
Sep 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Caitlin E MonaghanSusan L Ackerman

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Methods Mentioned

BETA
transgenic
RNAseq

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