Protein aggregation in retinal cells and approaches to cell protection
Protein aggregation in retinal cells and approaches to cell protection
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DOI：
10.1007/s10571-005-8474-1
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发表时间：
2005-09-01
影响因子：
4
通讯作者：
Surguchov, A
中科院分区：
文献类型：
--
作者：
Surgucheva, I;Ninkina, N;Surguchov, A
1. 视网膜营养不良 (RD) 包括一组临床和遗传异质性视网膜疾病，通常导致光感受器退化，进而导致视力损伤或丧失。尽管年龄相关性黄斑变性 (AMD) 和色素性视网膜炎 (RP) 是 RD 最常见的形式，但目前这两种疾病都没有有效的治疗方法。2．最近，由于蛋白质错误折叠和蛋白酶体抑制导致的异常蛋白质积累和聚集与 RD 的发病机制有关。在本文中，我们描述了几种因素对蛋白质聚集和感光细胞存活的影响。3．携带 P23H 突变的视紫红质的表达导致其在感光细胞核周区域的细胞内包涵体中积累。 β-和α-突触核蛋白以及热休克蛋白Hsp-70（但不是α-突触核蛋白）可以保护培养的眼细胞免受突变视蛋白积累的影响。这种效应可以通过它们的伴侣活动来解释。4． α-和γ-突触核蛋白的敲除不会影响视网膜的总体形态，但会在视网膜内部前状层中诱导酪氨酸羟化酶。司来吉兰 - 一种单胺氧化酶抑制剂，用于治疗帕金森病，可减少培养的视网膜色素上皮细胞 (APRE-19) 的细胞凋亡并增加活力。5。这些结果表明伴侣和司来吉兰可能被认为是保护眼细胞免受错误折叠和聚集蛋白积累的有希望的候选者。
1. Retinal dystrophies (RD) comprise a group of clinically and genetically heterogeneous retinal disorders, which typically result in the degeneration of photoreceptors followed by the impairment or loss of vision. Although age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are among the most common forms of RD, currently, there is no effective treatment for either disorder.2. Recently, abnormal protein accumulation and aggregation due to protein misfolding and proteasome inhibition have been implicated in the pathogenesis of RD. In this paper we describe effects of several factors on protein aggregation and survival of photoreceptor cells.3. Expression of rhodopsin carrying P23H mutation causes its accumulation in intracellular inclusion bodies in a perinuclear area of photoreceptor cells. beta- and alpha-synucleins and heat shock protein Hsp-70, but not alpha-synuclein, protect cultured ocular cells from mutant opsin accumulation. This effect might be explained by their chaperonic activity.4. Knock-out of alpha- and gamma-synucleins does not affect gross retinal morphology, but induces tyrosine hydroxylase in the inner prexiform layer of the retina. Selegiline-a monoamine oxidase inhibitor used for the treatment of Parkinson's disease, reduces apoptosis and increases viability in cultured retinal pigment epithelium cells (APRE-19).5. These results suggest that chaperones and selegiline may be considered promising candidates for the protection of ocular cells from the accumulation of misfolded and aggregated proteins.