Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance.
Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance.
复制标题
DOI：
10.1196/annals.1427.023
复制
发表时间：
2008-12
影响因子：
5.2
通讯作者：
Przedborski S
中科院分区：
文献类型：
--
作者：
Zhou C;Huang Y;Przedborski S
Parkinson disease (PD) is a common adult-onset neurodegenerative disorder. Typically, PD is a sporadic neurological disorder and over time, affected patients see their disability growing and their quality of life declining. Oxidative stress has been hypothesized to be linked to both the initiation and the progression of PD. Pre-clinical findings, from both in vitro and in vivo experimental models of PD, suggest that the neurodegenerative process starts with otherwise healthy neurons being hit by some etiological factors, which sets into motion a cascade of deleterious events. In these models, initial molecular alterations in degenerating dopaminergic neurons include increased formation of reactive oxygen species presumably originating from both inside and outside of the mitochondria. In the MPTP mouse model of PD, time-course experiments suggest that oxidative stress is an early event which may directly kill some of the dopaminergic neurons. In this model, it seems that oxidative stress may play a greater role in the demise of dopaminergic neurons indirectly by activating intracellular cell death-related molecular pathways. As the neurodegenerative process evolves in the MPTP mouse model, indices of neuroinflammation develop such as microglial activation. The latter increases the level of oxidative stress to which the neighboring compromised neurons are subjected to, thereby promoting their demise. However, these experimental studies have also shown that oxidative stress is not the sole deleterious factor implicated in the death of dopaminergic neurons. Should a similar multifactorial cascade underlie dopaminergic neuron degeneration in PD, then the optimal therapy for this disease may have to rely on a cocktail of agents, each targeting a different critical component of this hypothesized pathogenic cascade. If correct, this may be a reason why neuroprotective trials using a single agent such as an antioxidant have thus far generated disappointing results.
登录
查看更多内容
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
--
作者：
AMBANI, LM;VANWOERT, MH;MURPHY, S
通讯作者：
MURPHY, S
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
2.5
作者：
Abe, T;Isobe, C;Tohgi, H
通讯作者：
Tohgi, H
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT