A DJ-1 Based Peptide Attenuates Dopaminergic Degeneration in Mice Models of Parkinson's Disease via Enhancing Nrf2.
A DJ-1 Based Peptide Attenuates Dopaminergic Degeneration in Mice Models of Parkinson's Disease via Enhancing Nrf2.
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DOI：
10.1371/journal.pone.0127549
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Offen D
中科院分区：
文献类型：
--
作者：
Lev N;Barhum Y;Ben-Zur T;Aharony I;Trifonov L;Regev N;Melamed E;Gruzman A;Offen D
目前用于治疗帕金森氏症患者的药物可以在不改变神经退化过程的情况下缓解症状。我们的目的是研究使用DJ-1(Park7)作为治疗帕金森病的新靶点的可能性。我们设计了一种短肽，命名为ND-13。该肽由DJ-1蛋白的13个氨基酸片段组成，与来自细胞穿透蛋白TAT的7个氨基酸相连。我们使用帕金森氏病的体外和体内实验模型检验了ND-13的作用。我们证明了ND-13可以保护培养的细胞免受氧化和神经毒性损伤，减少活性氧的积累，激活保护性的红系2相关因子2系统，并提高细胞存活率。ND-13有力地减轻了多巴胺能系统功能障碍，并改善了6-羟基多巴胺帕金森病小鼠模型的行为结果，无论是在野生型还是在DJ-1基因敲除小鼠中。此外，ND-13还能恢复1-甲基-4-苯基-1，2，3，6-四氢吡啶模型小鼠的多巴胺含量。这些发现证实了DJ-1是帕金森氏病有希望的治疗靶点，并确定了一种具有临床潜力的新肽，这可能对更广泛的神经疾病具有重要意义，可能对神经科学产生重要影响。
Drugs currently used for treating Parkinson's disease patients provide symptomatic relief without altering the neurodegenerative process. Our aim was to examine the possibility of using DJ-1 (PARK7), as a novel therapeutic target for Parkinson's disease. We designed a short peptide, named ND-13. This peptide consists of a 13 amino acids segment of the DJ-1-protein attached to 7 amino acids derived from TAT, a cell penetrating protein. We examined the effects of ND-13 using in vitro and in vivo experimental models of Parkinson's disease. We demonstrated that ND-13 protects cultured cells against oxidative and neurotoxic insults, reduced reactive oxygen species accumulation, activated the protective erythroid-2 related factor 2 system and increased cell survival. ND-13 robustly attenuated dopaminergic system dysfunction and in improved the behavioral outcome in the 6-hydroxydopamine mouse model of Parkinson's disease, both in wild type and in DJ-1 knockout mice. Moreover, ND-13 restored dopamine content in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model. These findings validate DJ-1 as a promising therapeutic target in Parkinson's disease and identify a novel peptide with clinical potential, which may be significant for a broader range of neurological diseases, possibly with an important impact for the neurosciences.
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影响因子：
3.7
作者：
Lev N;Barhum Y;Lotan I;Steiner I;Offen D
通讯作者：
Offen D
DOI：
10.1073/pnas.0911175107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Hao, Ling-Yang;Giasson, Benoit I.;Bonini, Nancy M.
通讯作者：
Bonini, Nancy M.
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
14.8
作者：
Brewer, Gregory J.;Torricelli, John R.
通讯作者：
Torricelli, John R.
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M