Mitochondrial Complex I Reversible S-Nitrosation Improves Bioenergetics and Is Protective in Parkinson's Disease.

ABSTRACT:

Aims

This study was designed to explore the neuroprotective potential of inorganic nitrite as a new therapeutic avenue in Parkinson's disease (PD).

Results

Administration of inorganic nitrite ameliorates neuropathology in phylogenetically distinct animal models of PD. Beneficial effects are not confined to prophylactic treatment and also occur if nitrite is administered when the pathogenic cascade is already active. Mechanistically, the effect is mediated by both complex I S-nitrosation, which under nitrite administration is favored over formation of other forms of oxidation, and down-stream activation of the antioxidant Nrf2 pathway. Nitrite also rescues respiratory reserve capacity and increases proton leakage in LRRK2 PD patients' dermal fibroblasts.

Innovation

The

SUBMITTER: Milanese C 

PROVIDER: S-EPMC5749586 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature