Autophagy controls neonatal myogenesis by regulating the GH-IGF1 system through a NFE2L2-and DDIT3-mediated mechanism
AUTOPHAGY
Authors: Zecchini, Silvia; Giovarelli, Matteo; Perrotta, Cristiana; Morisi, Federica; Touvier, Thierry; Di Renzo, Ilaria; Moscheni, Claudia; Bassi, Maria Teresa; Cervia, Davide; Sandri, Marco; Clementi, Emilio; De Palma, Clara
Abstract
Macroautophagy/autophagy is emerging as an important process in adult muscle stem cells functions: it regulates metabolic reprogramming during activation from a quiescent state, maintains stemness and prevents senescence. We now show that autophagy is specifically required for neonatal myogenesis and muscle development. Specific deletion of Atg7 in PAX7(+) (paired box 7) precursors led in mice to a dwarf phenotype, with an effect restricted to the neonatal phase of muscle development. Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression. Lower levels of DDIT3 were responsible for reduced GHR expression leading to impaired local production of IGF1. Our results conclusively identify a novel autophagy-dependent pathway that regulates nSC behavior and indicate that autophagy is required for skeletal muscle development in the neonatal phase.
The NFE2L2 rs35652124 polymorphism and the risk of Parkinson's disease: a systematic review and meta-analysis
NEUROREPORT
Authors: Zhu, Mengru; Zhou, TingTing; Zu, Guo; Liang, ZhanHua
Abstract
The relationship between the nuclear factor erythroid-derived 2-like 2 (NFE2L2) rs35652124 (A/G) polymorphism and the risk of Parkinson's disease (PD) is controversial. To evaluate the association of the NFE2L2 rs35652124 polymorphism with the risk of PD, a meta-analysis was carried out. A total of 2264 PD cases and 2582 controls were included in the meta-analysis on the basis of strict inclusion and exclusion criteria. The pooled odds ratio (OR) and 95% confidence interval were calculated to assess the genetic association between the NFE2L2 rs35652124 polymorphism and the risk of PD. There was no significant association between rs35652124 and PD (G vs. A: OR = 1.001, P = 0.986; GG vs. AA: OR = 1.026, P = 0.785; GA vs. AA: OR = 1.023, P = 0.786; GG + GA vs. AA: OR = 1.224, P = 0.070; GG vs. GA + AA: OR = 0.994, P = 0.926). The data of our meta-analysis indicate that the G allele, GG, and GA genotype of the rs35652124 (A/G) polymorphism were not associated with the risk of PD. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.