The purpose of the studies outlined in this grant is to test the hypothesis that near infrared light emitting diode (NIR-LED) photobiomodulation will augment mitochondria! function and stimulate antioxidant protective pathways in cellular and animal models of Parkinson's disease (PD). A large and growing body of evidence supports a central role for mitochondrial dysfunction and oxidative stress in the pathogenesis of aging and neurodegenerative diseases including PD. Parkinson's disease is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of fibrous protein deposits consisting primarily of D-synuclein. The exact etiology of PD is unknown. There are inherited forms of PD that result from mutations in genes that code for a-synuclein. PD has also been associated with exposure to environmental toxins. The underlying pathological feature that is represented in both genetic and environmentally induced forms of PD is mitochondrial dysfunction resulting in increased production of reactive oxygen species followed by subsequent cell death of dopaminergic neurons located within the substanti nigra. Photobiomodulation by light in the red to near infrared range (670-880 nm) has been shown to improve recovery from ischemic injury in the heart, attenuate degeneration in the injured optic nerve and protect against mitochondrial dysfunction in the retina. Mechanistic studies in our laboratory and by other investigators have shown that that light in the far red to near-infrared range of the spectrum interacts with the enzyme, cytochrome oxidase, in mitochondria, triggering signaling mechanisms which result in improved energy metabolism, antioxidant production and cell survival. These studies will test the test the hypothesis that NIR-LED photobiomodulation (670 nm, energy density of 4 joules/cm2) will attenuate oxidative stress and cytotoxicity in cellular and transgenic mouse models of PD. Human neuroblastoma (SH-SY5Y) cells which stably overexpress wild type and mutant a-synuclein will be used as the cellular model and transgenic mice overexpressing human wild type a-synuclein will be used as the animal model, Information obtained from these studies may facilitate the development of NIR-LED as an innovative therapeutic approach for the treatment of PD.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AT003002-02
Application #
7230273
Study Section
Special Emphasis Panel (ZAT1-DB (21))
Program Officer
Sorkin, Barbara C
Project Start
2006-04-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2009-03-31
Support Year
2
Fiscal Year
2007
Total Cost
$182,770
Indirect Cost
Name
Medical College of Wisconsin
Department
Neurology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
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