Pleiotropic activity of systemically delivered angiogenin in the SOD1G93A mouse model

Neuropharmacology
Martin CrivelloJochen H M Prehn

Abstract

Loss-of-function mutations in the angiogenin (ANG) gene have been identified in familial and sporadic ALS patients. Previous work from our group identified human ANG (huANG) to protect motoneurons in vitro, and provided proof-of-concept that daily intraperitoneal (i.p.) huANG injections post-symptom onset increased lifespan and delayed disease progression in SOD1G93A mice. huANG's mechanism of action remains less well understood. Here, we implemented a preclinical in vivo design to validate our previous results, provide pharmacokinetic and protein distribution data after systemic administration, and explore potential pleiotropic activities of huANG in vivo. SOD1G93A mice (n = 45) and non-transgenic controls (n = 31) were sex- age- and litter-matched according to the 2010 European ALS/MND group guidelines, and treated with huANG (1 μg, i.p., 3 times/week) or vehicle from 90 days on. huANG treatment increased survival and delayed motor dysfunction as assessed by rotarod in SOD1G93A mice. Increased huANG serum levels were detectable 2 and 24 h after i.p. injection equally in transgenic and non-transgenic mice. Exogenous huANG localized to spinal cord astrocytes, supporting a glia-mediated, paracrine mechanism of action; uptake int...Continue Reading

Citations

Jan 23, 2020·Journal of Clinical Medicine·Tereza FilipiAnd Miroslava Anderova
Jul 9, 2020·Medicinal Research Reviews·Maria Zakharova
Aug 7, 2019·Disease Models & Mechanisms·Martin CrivelloJochen H M Prehn
Mar 8, 2020·Acta Pharmacologica Sinica·Jochen H M Prehn, Elisabeth Jirström
May 21, 2021·Eye and Brain·Vladislav O SoldatovAlexey V Deykin
Jul 28, 2021·Free Radical Biology & Medicine·J Jiménez-VillegasA I Rojo

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