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Mol Genet Metab. 2018 Nov;125(3):305-313. doi: 10.1016/j.ymgme.2018.08.002. Epub 2018 Aug 10.

Intranasal carnosine attenuates transcriptomic alterations and improves mitochondrial function in the Thy1-aSyn mouse model of Parkinson's disease.

Author information

1
Department of Environmental Health, University of Cincinnati, ML 670056, Cincinnati, OH 45267-0056, United States of America. Electronic address: Bermudmn@mail.uc.edu.
2
Department of Pediatrics, UC COM, Division of Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Avenue, MLC 7044, Cincinnati, OH 45229-3039, United States of America.
3
Department of Environmental Health, University of Cincinnati, ML 670056, Cincinnati, OH 45267-0056, United States of America. Electronic address: Marybeth.genter@uc.edu.

Abstract

Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). This study was designed to determine whether the dipeptide carnosine, which has been shown to protect against oxidative stress and mitochondrial dysfunction, would provide a beneficial effect on mitochondrial function in the Thy1-aSyn mouse model of PD. Thy1-aSyn mice, which overexpress wild-type human alpha-synuclein (aSyn), exhibit progressive non-motor and motor deficits as early as 2 months of age. Two-month old Thy1-aSyn mice and wild-type littermates were randomly assigned to treatment groups with intranasal (IN) and drinking water carnosine, with controls receiving 10 μl of sterile waster intranasally or carnosine-free drinking water, respectively. After two months of treatment, mice were euthanized, and the midbrain was dissected for the evaluation of the gene expression and mitochondrial function. Transcriptional deficiencies associated with the aSyn overexpression in Thy1-aSyn mice were related to ribosomal and mitochondrial function. These deficiencies were attenuated by IN carnosine administration, which increased the expression of mitochondrial genes and enhanced mitochondrial function. These results suggest a potential neuroprotective role for IN-carnosine in PD patients.

KEYWORDS:

Carnosine; Intranasal; Mitochondria; Parkinson's disease

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