Neuroprotective effect of overexpression of thioredoxin on photoreceptor degeneration in Tubby mice.

Abstract	The Tubby mouse is a phenotypic model for sensorineural deafness and retinal dystrophy including Usher syndrome type 1. Thioredoxin is a small 13kDa protein which, when ubiquitously expressed as a transgene in the mouse, provides protection against multiple disease states including light-induced and oxidative stress-induced neurodegeneration and is down-regulated in the Tubby retina. We tested if overexpression of human thioredoxin in the Tubby mouse inhibits retinal degeneration and loss of visual function. Electroretinography, immunocytochemistry, quantitative histology, RT-PCR and Western blots were used to obtain data which showed that thioredoxin overexpression prevented loss of photoreceptors and retinal function. Analysis of signal pathways showed that thioredoxin up-regulated neurotrophic factors BDNF and GDNF and activated survival signaling pathways Akt, Ras/Raf1/ and the ERKs while inhibiting the ASK1/JNK apoptosis pathway. Relationships between the Tubby gene, its pathological phenotype and regulation of the thioredoxin system remain to be established.
Authors	Li Kong, Xiaohong Zhou, Feng Li, Juni Yodoi, James McGinnis, Wei Cao
Journal	Neurobiology of disease (Neurobiol Dis) Vol. 38 Issue 3 Pg. 446-55 (Jun 2010) ISSN: 1095-953X [Electronic] United States
PMID	20298786 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Brain-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Proteins Tub protein, mouse Thioredoxins
Topics	Adaptor Proteins, Signal Transducing Animals Apoptosis (physiology) Brain-Derived Neurotrophic Factor (metabolism) Cell Count Cell Survival (physiology) Disease Models, Animal Glial Cell Line-Derived Neurotrophic Factor (metabolism) Hearing Loss, Sensorineural Humans Mice Mice, Inbred C57BL Mice, Transgenic Photoreceptor Cells, Vertebrate (metabolism, pathology) Proteins (genetics, metabolism) Retina (metabolism, pathology) Retinal Degeneration (metabolism, pathology) Signal Transduction Thioredoxins (metabolism) Vision, Ocular (physiology)

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