RRC ID 50492
著者 Yeh PA, Liu YH, Chu WC, Liu JY, Sun YH.
タイトル Glial expression of disease-associated poly-glutamine proteins impairs the blood-brain barrier in Drosophila.
ジャーナル Hum Mol Genet
Abstract Expansion of poly-glutamine (polyQ) stretches in several proteins has been linked to neurodegenerative diseases. The effects of polyQ-expanded proteins on neurons have been extensively studied, but their effects on glia remain unclear. We found that expression of distinct polyQ proteins exclusively in all glia or specifically in the blood-brain barrier (BBB) and blood-retina barrier (BRB) glia caused cell-autonomous impairment of BBB/BRB integrity, suggesting that BBB/BRB glia are most vulnerable to polyQ-expanded proteins. Furthermore, we also found that BBB/BRB leakage in Drosophila is reflected in reversed waveform polarity on the basis of electroretinography (ERG), making ERG a sensitive method to detect BBB/BRB leakage. The polyQ-expanded protein Atxn3-84Q forms aggregates, induces BBB/BRB leakage, restricts Drosophila lifespan and reduces the level of Repo (a pan-glial transcriptional factor required for glial differentiation). Expression of Repo in BBB/BRB glia can rescue BBB/BRB leakage, suggesting that the reduced expression of Repo is important for the effect of polyQ on BBB/BRB impairment. Coexpression of the chaperon HSP40 and HSP70 effectively rescues the effects of Atxn3-84Q, indicating that polyQ protein aggregation in glia is deleterious. Intriguingly, coexpression of wild-type Atxn3-27Q can also rescue BBB/BRB impairment, suggesting that normal polyQ protein may have a protective function.
巻・号 27(14)
ページ 2546-2562
公開日 2018-7-15
DOI 10.1093/hmg/ddy160
PII 4991969
PMID 29726932
MeSH Animals Ataxin-3 / genetics* Blood-Brain Barrier / metabolism Blood-Brain Barrier / pathology Blood-Retinal Barrier / metabolism Blood-Retinal Barrier / pathology Disease Models, Animal Drosophila Proteins / genetics Drosophila melanogaster / genetics Electroretinography Eye / ultrastructure Gene Expression Regulation HSP40 Heat-Shock Proteins / genetics HSP70 Heat-Shock Proteins / genetics Humans Neurodegenerative Diseases / genetics* Neurodegenerative Diseases / physiopathology Neuroglia / metabolism* Neuroglia / pathology Neurons / metabolism Neurons / pathology Peptides / genetics*
IF 5.101
引用数 4
リソース情報
ショウジョウバエ 4322R-2