Glutathione depletion and overproduction both initiate degeneration of nigral dopaminergic neurons
Clicks: 191
ID: 114415
2010
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Emerging Content
30.0
/100
191 views
38 readers
AI Quality Assessment
Not analyzed
Readership in this journal
EmergingRanked #171 of 438 articles by views in acta neuropathologica
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 438 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Parkinson’s disease is a neurodegenerative disorder characterized by severe motor deficits mainly due to degeneration of dopaminergic neurons in the substantia nigra. Decreased levels of the cell’s most important anti-oxidant, glutathione, have been detected in nigral neurons of Parkinson patients, but it is unknown if they are the cause or merely the consequence of the disease. To elucidate if glutathione depletion causes selective degeneration of nigral dopaminergic neurons, we down-regulated glutathione synthesis in different brain areas of adult rats by a viral vector-based RNAi approach. Decreased glutathione synthesis resulted in progressive degeneration of nigral dopaminergic neurons, while extra-nigral and striatal neurons were significantly less vulnerable. Degeneration of dopaminergic neurons was accompanied by progressive protein aggregate formation and functional motor deficits and was partially rescued by α-synuclein. That the survival of nigral dopaminergic neurons depends on the precise control of glutathione levels was further demonstrated by significant degeneration induced through moderate overproduction of glutathione. Over-expression of either of the two subunits of glutamate–cysteine ligase induced aberrant glutathiolation of cellular proteins and significant degeneration of dopaminergic neurons. Thus, while glutathione depletion was demonstrated to be a selective trigger for dopaminergic neuron degeneration, a glutathione replacement approach as a potential treatment option for Parkinson’s patients must be considered with great care. In conclusion, our data demonstrate that survival of nigral dopaminergic neurons crucially depends on a tight regulation of their glutathione levels and that the depleted glutathione content detected in the brains of Parkinson’s disease patients can be a causative insult for neuronal degeneration.
| Reference Key |
garrido2010actaglutathione
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Manuel Garrido;Yuliya Tereshchenko;Zinayida Zhevtsova;Grit Taschenberger;Mathias Bähr;Sebastian Kügler;Manuel Garrido;Yuliya Tereshchenko;Zinayida Zhevtsova;Grit Taschenberger;Mathias Bähr;Sebastian Kügler; |
| Journal | acta neuropathologica |
| Year | 2010 |
| DOI |
doi:10.1007/s00401-010-0791-x
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.