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

Authors: Bermúdez, Mei-Ling; Skelton, Matthew R; Genter, Mary Beth

Published In Mol Genet Metab, (2018 Nov)

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.

PubMed ID: 30146452 Exiting the NIEHS site

MeSH Terms: Administration, Intranasal; Animals; Carnosine/administration & dosage*; Corpus Striatum/drug effects; Corpus Striatum/pathology; Disease Models, Animal; Humans; Mice; Mice, Transgenic; Mitochondria/drug effects; Mitochondria/genetics; Parkinson Disease/drug therapy*; Parkinson Disease/genetics; Parkinson Disease/pathology; Thy-1 Antigens/genetics*; Transcriptome/drug effects; alpha-Synuclein/genetics*

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Last Reviewed: October 07, 2024