| Literature DB >> 27516389 |
Lijuan Zhang1,2,3, Sally Justus1,2, Yu Xu1,2,4, Tamara Pluchenik1,2, Chun-Wei Hsu1,2, Jin Yang1,2,5, Jimmy K Duong6, Chyuan-Sheng Lin7, Yading Jia3, Alexander G Bassuk8, Vinit B Mahajan9,10, Stephen H Tsang11,2.
Abstract
Retinitis pigmentosa (RP) is an incurable neurodegenerative condition featuring photoreceptor death that leads to blindness. Currently, there is no approved therapeutic for photoreceptor degenerative conditions like RP and atrophic age-related macular degeneration (AMD). Although there are promising results in human gene therapy, RP is a genetically diverse disorder, such that gene-specific therapies would be practical in a small fraction of patients with RP. Here, we explore a non-gene-specific strategy that entails reprogramming photoreceptors towards anabolism by upregulating the mechanistic target of rapamycin (mTOR) pathway. We conditionally ablated the tuberous sclerosis complex 1 (Tsc1) gene, an mTOR inhibitor, in the rods of the Pde6bH620Q/H620Q preclinical RP mouse model and observed, functionally and morphologically, an improvement in the survival of rods and cones at early and late disease stages. These results elucidate the ability of reprogramming the metabolome to slow photoreceptor degeneration. This strategy may also be applicable to a wider range of neurodegenerative diseases, as enhancement of nutrient uptake is not gene-specific and is implicated in multiple pathologies. Enhancing anabolism promoted neuronal survival and function and could potentially benefit a number of photoreceptor and other degenerative conditions.Entities:
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Year: 2016 PMID： 27516389 PMCID： PMC5291198 DOI： 10.1093/hmg/ddw256
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150