@article {2019,
	title = {Calpains as mechanistic drivers and therapeutic targets for ocular disease.},
	journal = {Trends Mol Med},
	volume = {28},
	year = {2022},
	month = {2022 08},
	pages = {644-661},
	abstract = {<p>Ophthalmic neurodegenerative diseases encompass a wide array of molecular pathologies unified by calpain dysregulation. Calpains are calcium-dependent proteases that perpetuate cellular death and inflammation when hyperactivated. Calpain inhibition trials in other organs have faced pharmacological challenges, but the eye offers many advantages for the development and testing of targeted molecular therapeutics, including small molecules, peptides, engineered proteins, drug implants, and gene-based therapies. This review highlights structural mechanisms underlying calpain activation, distinct cellular expression patterns, and in vivo models that link calpain hyperactivity to human retinal and developmental disease. Optimizing therapeutic approaches for calpain-mediated eye diseases can help accelerate clinically feasible strategies for treating calpain dysregulation in other diseased tissues.</p>
},
	keywords = {Calcium, Calpain, Cell Death, Humans, Retina},
	issn = {1471-499X},
	doi = {10.1016/j.molmed.2022.05.007},
	author = {Vu, Jennifer T and Wang, Elena and Wu, Jolan and Sun, Young Joo and Velez, Gabriel and Bassuk, Alexander G and Lee, Soo Hyeon and Mahajan, Vinit B}
}
@article {641,
	title = {Reprogramming towards anabolism impedes degeneration in a preclinical model of retinitis pigmentosa.},
	journal = {Hum Mol Genet},
	volume = {25},
	year = {2016},
	month = {2016 10 01},
	pages = {4244-4255},
	abstract = {<p>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 Pde6bpreclinical 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.</p>},
	keywords = {Animals, Cell Death, Cellular Reprogramming, Cone-Rod Dystrophies, Disease Models, Animal, Humans, Macular Degeneration, Metabolism, Mice, Photoreceptor Cells, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Retinitis Pigmentosa, TOR Serine-Threonine Kinases, Tumor Suppressor Proteins},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddw256},
	author = {Zhang, Lijuan and Justus, Sally and Xu, Yu and Pluchenik, Tamara and Hsu, Chun-Wei and Yang, Jin and Duong, Jimmy K and Lin, Chyuan-Sheng and Jia, Yading and Bassuk, Alexander G and Mahajan, Vinit B and Tsang, Stephen H}
}
