Brendan J. Quirk¹, Kristina D. DeSmet^2,3, Michele Henry ^1,4, Ellen Buchmann¹, Margaret Wong-Riley⁵, Janis T. Eells², Harry T. Whelan¹

1Department of Neurology, Medical College of Wisconsin, 8701 W. Watertown Plank Rd, Milwaukee, WI, 53226, USA, ²Department of Health Sciences, University of Wisconsin-Milwaukee, 2400 E. Hartford Ave, Milwaukee, WI, 53201, USA, ³The Hamner-UNC Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Six Davis Drive, Research Triangle Park, NC, 27709, USA, ⁴Marshfield Clinic Research Foundation, (MCRF) 1000 N. Oak Ave., Laird South-ML1 Marshfield, WI 54449, ⁵Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 W. Watertown Plank Rd, Milwaukee, WI, 53226, USA

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Mitochondrial dysfunction

4. NIR light therapy

5. Complex I inhibitors

6. Cell culture models

6.1. Primary neurons

6.2. Mutant neuroblastoma cells

6.3. Cybrid cells

7. Animal models

7.1. MPTP mice

7.2. Transgenic mice

8. Perspective

9. Acknowledgments

10. References

1. ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder that affects large numbers of people, particularly those of a more advanced age. Mitochondrial dysfunction plays a central role in PD, especially in the electron transport chain. This mitochondrial role allows the use of inhibitors of complex I and IV in PD models, and enhancers of complex IV activity, such as NIR light, to be used as possible therapy. PD models fall into two main categories; cell cultures and animal models. In cell cultures, primary neurons, mutant neuroblastoma cells, and cell cybrids have been studied in conjunction with NIR light. Primary neurons show protection or recovery of function and morphology by NIR light after toxic insult. Neuroblastoma cells, with a gene for mutant alpha-synuclein, show similar results. Cell cybrids, containing mtDNA from PD patients, show restoration of mitochondrial transport and complex I and IV assembly. Animal models include toxin-insulted mice, and alpha-synuclein transgenic mice. Functional recovery of the animals, chemical and histological evidence, and delayed disease progression show the potential of NIR light in treating Parkinson's disease.