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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Acknowledgements
This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) under Grant Number 16/RC/3948 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners and by the Joint Programme in Neurodegeneration Research (JPND) project RNA-NEURO supported by SFI (17/JPND/3455). EJ is supported by a StAR International PhD Scholarship from the Royal College of Surgeons in Ireland.
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JHMP is a beneficiary of a patent relating to the use of angiogenin as a diagnostic and therapeutic for ALS and other neurodegenerative disorders. EJ declares no competing interest.
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Prehn, J.H.M., Jirström, E. Angiogenin and tRNA fragments in Parkinson’s disease and neurodegeneration. Acta Pharmacol Sin 41, 442–446 (2020). https://doi.org/10.1038/s41401-020-0375-9
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DOI: https://doi.org/10.1038/s41401-020-0375-9
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