Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons.
Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons.
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DOI：
10.18632/aging.101045
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发表时间：
2016-09-23
期刊：
影响因子：
--
通讯作者：
Walton JP
中科院分区：
文献类型：
--
作者：
Frisina RD;Ding B;Zhu X;Walton JP
年龄相关性听力损失(ARHL) -老年性耳聋-是最常见的神经退行性疾病和老年人的头号沟通障碍；影响着全世界数亿人。它的患病率接近心血管疾病和关节炎，可能是痴呆的前兆。听觉感知功能障碍已被充分了解，但对ARHL的生物学基础的了解仍有所欠缺。令人惊讶的是，没有fda批准的治疗药物。根据我们之前对人类受试者的研究，我们发现了血清醛固酮水平与ARHL严重程度之间的关系，我们用醛固酮治疗中年小鼠，在所有哺乳动物中，醛固酮通常会随着年龄的增长而下降。我们发现，与未接受醛固酮治疗的小鼠相比，接受醛固酮治疗的小鼠的听力阈值和超阈反应显著改善。就这种治疗效果的细胞和分子机制而言，其他实验显示螺旋神经节细胞存活率显著提高，矿皮质激素受体通过翻译后蛋白修饰上调，醛固酮治疗阻断了与年龄相关的内源性和外源性凋亡途径。综上所述，这些新发现为开发第一种预防ARHL进展的药物铺平了道路。
Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL.
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影响因子：
3.7
作者：
Hall JW;Buss E;Grose JH;Roush PA
通讯作者：
Roush PA
DOI：
10.1016/j.jconrel.2013.11.021
发表时间：
2014-01-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Borkholder DA;Zhu X;Frisina RD
通讯作者：
Frisina RD
DOI：
10.18632/aging.100927
发表时间：
2016-04
期刊：
Aging
影响因子：
--
作者：
Ding D;Jiang H;Chen GD;Longo-Guess C;Muthaiah VP;Tian C;Sheppard A;Salvi R;Johnson KR
通讯作者：
Johnson KR
影响因子：
2.8
作者：
Frisina, Robert D.;Walton, Joseph P.
通讯作者：
Walton, Joseph P.
DOI：
10.1073/pnas.0503878102
发表时间：
2006-01-03
影响因子：
11.1
作者：
Berger, S;Wolfer, DP;Schütz, G
通讯作者：
Schütz, G