![]() ![]() These mutations are grouped into classes according to their biochemical characteristics among them, class II mutations affect the structural stability of RHO protein and are most numerous. ![]() More than 150 mutations have been identified in the RHO gene that causes adRP, and only 4 mutations cause autosomal recessive RP ( ). As the most abundant protein in rod cells, RHO misfolding caused by genetic mutation leads to a tremendous load on proteostasis ( 12, 13). RHO is the visual pigment protein located in rod outer segments (OS ref. Although gene therapies have been successful in treating Leber congenital amaurosis ( 7– 10) and show promise for treating some genotypes of RP, no pharmacological treatments are available for RP. RHODOPSIN ( RHO) gene mutations account for about 25% of all autosomal dominant RP (adRP ref. 6), a progressive retinal degeneration due to loss of rod photoreceptors. Misfolded proteins are involved in the etiology of many diseases, including neural degenerations ( 1, 2), lysosome storage disorders ( 3), cystic fibrosis ( 4), and type II diabetes ( 5), as well as visual disorders including retinitis pigmentosa (RP ref. Collectively, we provide proof of principle that nonretinoid chaperones are promising drug candidates in treating RHO-associated RP. In vivo, intravitreal injection of YC-001 or F5257-0462 microparticles in PBS shows that F5257-0462 has a higher efficacy in preserving photoreceptor function and delaying photoreceptor death in Rho P23H/+ mice. Similarly, F5257-0462 also protects photoreceptors in Rho P23H/+ retinal explants. Interestingly, YC-001 ameliorated retinal immune responses and reduced the number of microglia/macrophages in the Rho P23H/+ retinal explants. Furthermore, using retinal explant culture, we show that YC-001 improves retinal proteostasis by supporting RHO homeostasis in Rho P23H/+ mouse retinae, which results in thicker outer nuclear layers (ONL), indicating delayed photoreceptor degeneration. ![]() Here, we profile the chaperone activities of these molecules toward the cell-surface level of 27 RP-causing human RHO mutants in NIH3T3 cells. We previously identified nonretinoid chaperones of RHO, including YC-001 and F5257-0462, by small-molecule high-throughput screening. RHO protein misfolding leads to disturbed proteostasis and the death of rod photoreceptors, resulting in decreased vision. Use this map to explore the estimated global population density (people per square kilometer) in 2020.Rhodopsin-associated ( RHO-associated) retinitis pigmentosa (RP) is a progressive retinal disease that currently has no cure. This means urban areas could appear to have fewer people than they really do, while rural areas would seem to have more. All of these areas have a vastly different population density, but they are averaged together. Whereas at a larger scale, such as the state, region, or province level, population density could vary widely as it includes a mix of urban, suburban, and rural places. Population density is most effective in small- scale places-cities or neighborhoods-where people are evenly distributed. While a useful tool for decision and policymakers, it is important to understand the limitations of population density. Infectious disease scientists use these maps to understand the spread of infectious disease, a topic that has become critical after the COVID-19 global pandemic. Experts can use this information to inform decisions around resource allocation, natural disaster relief, and new infrastructure projects. Understanding and mapping population density is important. Population density is the average number of people per unit, usually miles or kilometers, of land area. ![]() This has resulted in an increase in population density for these cities, which are now forced to expand in order to accommodate the growing population. Job opportunities in large cities have caused an influx of people to these already packed locations. In the last century, the global population has increased by billions of people. ![]()
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