Is Mitochondrial Hemoglobin Reduced in Parkinson’s Disease Brain?

Objective/Rationale: 
Mitochondria are undergoing scrutiny by researchers trying to understand Parkinson’s disease (PD). We have discovered that the oxygen-carrying protein hemoglobin is found in neuronal mitochondria. Our initial data show a significant reduction in mitochondrial hemoglobin in PD brain when compared with control brains. Further confirmation and a better characterization of this phenomenon, in greater numbers of PD brains, will open a new avenue of inquiry in PD research.

Project Description:
We will examine hemoglobin protein in post-mortem PD and control brains. The brain samples will be grouped according to age of PD onset and duration of disease. We are able to obtain these fully consented tissues from local and other UK brain banks operating under the National Human Tissue Act. Relative levels of hemoglobin will be measured in different parts of the brain cells, including the mitochondria, using antibodies designed to recognize this protein. In addition, we will use an electron microscope to examine the precise location of hemoglobin in the most well-preserved specimens. During the course of our study we will survey mitochondrial hemoglobin in several different brain regions including frontal lobe, substantia nigra and cerebellum.

Relevance to Diagnosis/Treatment of Parkinson’s disease:
Understanding changes in a protein that carries oxygen and resides in the mitochondria could give insight into why these cell components become dysfunctional. Examination of mitochondrial hemoglobin may also enlighten the field in matters of observed oxidative stress and iron accumulation in Parkinson’s.

Anticipated Outcome:          
Successful completion of our study will provide a strong basis for looking carefully at hemoglobin as a potential target for therapy in Parkinson’s. We will collect sufficient data to prove unequivocally whether there is a change in mitochondrial hemoglobin levels associated with disease, and we will obtain information about how these changes are related to disease. This work will form a springboard from which we can ask more specific questions about changes in mitochondrial hemoglobin and how we might use hemoglobin as a biomarker or therapeutic target.