The Reversible Carnitine Palmitoyltransferase 1 Inhibitor (Teglicar) Ameliorates the Neurodegenerative Phenotype in a Drosophila Huntington’s Disease Model by Acting on the Expression of Carnitine-Related Genes

Molecules

Yulii V. Shidlovskii¹  Carla Bertapelle²  Filomena Anna Digilio²  Maria Rosaria Carillo²  Nunzio Antonio Cacciola²  Gianfranco Peluso² 

[1] Department of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia;Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-CNR, Via Pietro Castellino 111, 80131 Naples, Italy;

关键词: Drosophila melanogaster;    Huntington’s disease;    neurodegeneration;    L-carnitine;    carnitine shuttle;    mitochondria;   

DOI  :  10.3390/molecules27103125

来源: DOAJ

【 摘 要 】

Huntington’s disease (HD) is a dramatic neurodegenerative disorder caused by the abnormal expansion of a CAG triplet in the huntingtin gene, producing an abnormal protein. As it leads to the death of neurons in the cerebral cortex, the patients primarily present with neurological symptoms, but recently metabolic changes resulting from mitochondrial dysfunction have been identified as novel pathological features. The carnitine shuttle is a complex consisting of three enzymes whose function is to transport the long-chain fatty acids into the mitochondria. Here, its pharmacological modification was used to test the hypothesis that shifting metabolism to lipid oxidation exacerbates the HD symptoms. Behavioural and transcriptional analyses were carried out on HD Drosophila model, to evaluate the involvement of the carnitine cycle in this pathogenesis. Pharmacological inhibition of CPT1, the rate-limiting enzyme of the carnitine cycle, ameliorates the HD symptoms in Drosophila, likely acting on the expression of carnitine-related genes.

【 授权许可】

Unknown