Targeting mitochondrial complex I dependent NAD+ generation in Parkinson's Disease

Project: Research project

Project Details

Description

Study Rationale:
In two or three sentences, describe the background and scientific rationale for this project. Approximately 100 words

Mitochondrial complex I inhibition is one of the major mechanisms in the development of Parkinson’s disease (PD). We have uncovered that decreasing mitochondrial complex I function results in diminished NAD+ which can trigger the production of a neurotoxic metabolite L-2hydroxyglutarate (L-2HG).

Hypothesis:
In one sentence, describe the question this study seeks to answer or the theory you hope to prove. Approximately 50 words

We hypothesize that decreased NAD+ due to mitochondrial complex I dysfunction triggers the accumulation of neurotoxic metabolite L-2HG in dopaminergic neurons to cause PD-like pathology in mice.

Study Design:
In two or three sentences, in lay-oriented language, describe how you will carry out the project. Approximately 100 words

The yeast NDI1 protein can rescue the loss of mitochondrial complex I NAD+ regeneration resulting in decreased L-2HG levels. The expression of L-2HGDH can also decrease L-2HG levels. We propose to conditionally overexpress NDI1 or L-2HGDH to
StatusActive
Effective start/end date9/1/218/31/23

Funding

  • The Michael J Fox Foundation for Parkinson's Research (MJFF-019886)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.