Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population

Zhou, Xu‐jie; Lu, Xuedong; Lv, Jicheng; Yang, Haizhen; Qin, Lian-xiang; Zhao, Ming‐Hui; Su, Yin; Li, Zhanguo; Zhang, Hong

doi:10.1136/ard.2010.140111

Cited by 205 publications

(199 citation statements)

References 52 publications

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“…Autophagy is tightly linked with auto-immune diseases, including MS [15][16][17] . The extracellular matrix molecule fibronectin aggregates in chronically demyelinating MS and the relapsig phase of EAE; it may be resistant to degradation and affect the remyelination process [18] .…”

Section: Introductionmentioning

confidence: 99%

“…The frail neurons die when they are exposed to the infl ammatory environment. Pro-infl ammatory factors such as IL17 impair the differentiation of oligodendrocyte progenitor cells (OPCs) in MS [14] .Autophagy is tightly linked with auto-immune diseases, including MS [15][16][17] . The extracellular matrix molecule fibronectin aggregates in chronically demyelinating MS and the relapsig phase of EAE; it may be resistant to degradation and affect the remyelination process [18] .…”

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confidence: 99%

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Role of autophagy in the pathogenesis of multiple sclerosis

Liang

2015

Neurosci. Bull.

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Autophagy plays an important role in maintaining the cellular homeostasis. One of its functions is to degrade unnecessary organelles and proteins for energy recycling or amino-acids for cell survival. Ablation of autophagy leads to neurodegeneration. Multiple sclerosis (MS), a permanent neurological impairment typical of chronic inflammatory demyelinating disorder, is an auto-immune disease of the central nervous system (CNS). Autophagy is tightly linked to the innate and adaptive immune systems during the autoimmune process, and several studies have shown that autophagy directly participates in the progress of MS or experimental autoimmune encephalomyelitis (EAE, a mouse model of MS). Dysfunction of mitochondria that intensively infl uences the autophagy pathway is one of the important factors in the pathogenesis of MS. Autophagy-related gene (ATG) 5 and immune-related GTPase M (IRGM) 1 are increased, while ATG16L2 is decreased, in T-cells in EAE and active relapsing-remitting MS brains. Administration of rapamycin, an inhibitor of mammalian target of rapamycin ( mTOR), ameliorates relapsing-remitting EAE. Infl ammation and oxidative stress are increased in MS lesions and EAE, but Lamp2 and the LC3-II/LC3-I ratio are decreased. Furthermore, autophagy in various glial cells plays important roles in regulating neuro-infl ammation in the CNS, implying potential roles in MS. In this review, we discuss the role of autophagy in the peripheral immune system and the CNS in neuroinfl ammation associated with the pathogenesis of MS. Keywords: autophagy; multiple sclerosis; neuro-infl ammation ·Review· IntroductionAutophagy, a lysosome-dependent degradation pathway, contributes to maintaining cellular homeostasis. Clearance of long-lived proteins, unnecessary organelles, and aggregate-prone proteins is mainly executed by autophagy for recycling cellular materials [1] . There are three subtypes of autophagy, macroautophagy, chaperone-mediated autophagy (CMA), and mitophagy. Macroautophagy is the major type for selective degradation of protein aggregates or misfolded proteins. The ubiquitin-labeled proteins are recognized by autophagy receptors, such as p62, neighbor of BRCA1 gene 1 (NBR1), and NIP3-like protein X (NIX), to form autophagosomes that then fuse with lysosomes for degradation. Many autophagy-related genes function during this process, such as Unc51-like kinase (ULK1) and autophagy-related gene (ATG) 5. Mammalian target of rapamycin (mTOR) represses autophagy by regulating ULK1 phosphorylation, while AMPK activates this process.CMA mediates the degradation of large molecular-weight proteins containing the KFERQ motif recognized by heat shock cognate protein of 70 kDa (HSC70). The substrate is then escorted to lysosome-associated membrane protein 2 (LAMP2A) for lysosomal degradation. Mitophagy is responsible for the degradation of damaged mitochondria.Parkin and PINK1 play critical roles in this process [2] . More Neurosci Bull August 1, 2015, 31(4): 435-444 436 attention has been paid to autophagy in the path...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Role of autophagy in the pathogenesis of multiple sclerosis

Liang

2015

Neurosci. Bull.

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“…Dans une pathologie auto-immune systémique -le lupus érythémateux disséminé (LED) 6 -, l'identification de polymorphismes génétiques dans la région du gène ATG5, corrélés avec le développement de la pathologie, a conduit à s'interroger sur l'implication de l'autophagie [42]. Même si la signification fonctionnelle de ces polymorphismes est encore peu documentée, des auteurs ont proposé l'existence d'une corrélation entre une des variantes de la maladie et une plus forte expression transcriptionnelle d'ATG5 [43]. Un des polymorphismes d'ATG5 est également associé au développement de l'asthme, une autre pathologie caractérisée par une hyperactivation du système immunitaire [44].…”

Section: Autophagie Des Lymphocytes Et Physiopathologieunclassified

L’autophagie et l’homéostasie des lymphocytes T et B

et al. 2016

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“…While, the ATG5 candidate gene function is still obscure and needed to be determined however, both known to play important roles in immunity. Genome-wide association studies suggested the PRDM1-ATG5 gene region as a systemic lupus erythematosus (SLE)-associated locus both in Caucasian and Asian populations, presumably through upregulating gene expression (Zhou, 2011;). Significant positive correlations with ATG5 expression were identified, suggesting ATG5 as a candidate gene in the region .…”

Section: Pr Domain Containing 1 With Znf Domain -Apg5 Autophagy 5-limentioning

confidence: 99%