Nitrosative stress in Parkinson's disease.
Morgan G Stykel1, Scott D Ryan2,3
1The Department of Molecular and Cellular Biology, The University of Guelph, Guelph, ON N1G 2W1, ON, Canada.
NPJ Parkinson'S Disease
|August 11, 2022
Summary
Reactive nitrogen species (RNS) contribute to the loss of dopaminergic neurons in Parkinson's Disease (PD). Targeting RNS, particularly through S-nitrosylation, shows therapeutic promise for early-stage PD patients.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Parkinson's Disease (PD) involves dopaminergic neuron loss in the nigral-striatal pathway.
- Reactive nitrogen species (RNS), including nitric oxide (NO), are implicated in this neurodegeneration.
Purpose of the Study:
- To review the mechanisms by which RNS contribute to dopaminergic neuron loss in PD.
- To investigate RNS accumulation as a central signaling event in PD pathogenesis.
- To explore therapeutic strategies targeting RNS.
Main Methods:
- Review of cellular sources of RNS in PD (nNOS, iNOS, nitrate/nitrite reduction).
- Analysis of RNS-induced protein post-translational modifications, specifically S-nitrosylation.
- Examination of RNS impact on alpha-synuclein (aSyn) and PD-related cellular dysfunctions.
Main Results:
- RNS sources are upregulated in PD, leading to RNS accumulation.
- Over one-third of Lewy Body proteins are S-nitrosylated, causing deleterious neuronal effects.
- Nitration of alpha-synuclein (aSyn) promotes misfolding and toxicity; RNS modulates axo-dendritic, mitochondrial, and dopamine dysfunctions.
Conclusions:
- RNS accumulation is a key factor in PD neurodegeneration.
- Targeting RNS, specifically protein S-nitrosylation, demonstrates therapeutic potential in clinical trials for early PD.
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