Therapeutic efficacy of near-infrared light for the treatment of Parkinson's disease.

摘要

A large body of evidence supports a central role for mitochondrial dysfunction and genetic susceptibility in the pathogenesis of Parkinson's disease (PD). Support for this concept is derived from the identification of inherited forms of PD that result from mutations in genes that code for alpha-synuclein. PD has also been associated with exposure to environmental toxins including pesticides which are either oxidants or mitochondrial toxins. The underlying pathological feature 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 in the substantia nigra. Irradiation by far-red to near-infrared (NIR) (630 to 1000 nm) light has been shown to enhance mitochondrial energy production and promote cellular survival following a mitochondrial insult. The present studies test the hypothesis that NIR light treatment will augment mitochondrial function and stimulate cytoprotective pathways in cellular and animal models of Parkinson's disease. In vitro, studies utilized SH-SY5Y human neuroblastoma cells transfected with the A30P alpha-synuclein mutation exposed to MPP+, a complex I inhibitor. NIR treatment promoted cell survival in SH-SY5Y A3OP cells by mechanisms that include enhanced energy metabolism resulting from increased cytochrome oxidase activity, reduced oxidative stress, altered expression of apoptotic-linked proteins and prevention of alpha-synuclein protein expression. In vivo studies tested the hypothesis that NIR pre-treatment would attenuate the toxic effects of acute MPTP exposure on motor activity in C57BL mice. NIR pre-treatment attenuated behavioral deficits, specifically loss of movement and time spent moving, resulting from acute MPTP exposure. A second series of in vivo studies tested the hypothesis that NIR treatment would attenuate the toxic effect of A53T mutant alpha-synuclein in transgenic mice. These mice develop a late-onset neurodegenerative disorder that coincides with alpha-synuclein aggregate formation. NIR treatment starting at 8 weeks of age resulted in reduced incidence, delayed onset of disease phenotype, reduced severity of phenotype, increased dopamine content in the striatum and altered apoptotic-linked protein expression in the striatum. These findings support the potential for NIR treatment as a novel therapy for the attenuation of dopaminergic neuronal cell death in PD patients.