Daf-2 Signaling Modifies Mutant SOD1 Toxicity in C. elegans

被引：34

作者：

Boccitto, Marco ^{[1
,2
]}

Lamitina, Todd ^{[3
]}

Kalb, Robert G. ^{[1
,2
,4
]}

机构：

[1] Childrens Hosp Philadelphia Res Inst, Div Neurol, Dept Pediat, Philadelphia, PA USA

[2] Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

来源：

PLOS ONE | 2012年 / 7卷 / 03期

基金：

美国国家卫生研究院;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE; PROTEIN AGGREGATION; HEXANUCLEOTIDE REPEAT; LIFE-SPAN; MUTATIONS; LONGEVITY; INSULIN/IGF-1; METABOLISM; PROHIBITIN;

D O I：

10.1371/journal.pone.0033494

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS.

引用

页数：8

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