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The Carnitine Palmitoyl Transferase (CPT) System and Possible Relevance for Neuropsychiatric and Neurological Conditions

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Abstract

The carnitine palmitoyl transferase (CPT) system is a multiprotein complex with catalytic activity localized within a core represented by CPT1 and CPT2 in the outer and inner membrane of the mitochondria, respectively. Two proteins, the acyl-CoA synthase and a translocase also form part of this system. This system is crucial for the mitochondrial beta-oxidation of long-chain fatty acids. CPT1 has two well-known isoforms, CPT1a and CPT1b. CPT1a is the hepatic isoform and CPT1b is typically muscular; both are normally utilized by the organism for metabolic processes throughout the body. There is a strong evidence for their involvement in various disease states, e.g., metabolic syndrome, cardiovascular diseases, and in diabetes mellitus type 2. Recently, a new, third isoform of CPT was described, CPT1c. This is a neuronal isoform and is prevalently localized in brain regions such as hypothalamus, amygdala, and hippocampus. These brain regions play an important role in control of food intake and neuropsychiatric and neurological diseases. CPT activity has been implicated in several neurological and social diseases mainly related to the alteration of insulin equilibrium in the brain. These pathologies include Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Evolution of both Parkinson’s disease and Alzheimer’s disease is in some way linked to brain insulin and related metabolic dysfunctions with putative links also with the diabetes type 2. Studies show that in the CNS, CPT1c affects ceramide levels, endocannabionoids, and oxidative processes and may play an important role in various brain functions such as learning.

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Authors and Affiliations

  1. Research, Innovation and Development, Sigma-tau Health Science International BV, Utrecht, Netherlands

    Ashraf Virmani, Luigi Pinto, Otto Bauermann & Saf Zerelli

  2. Sigma-tau SpA, Pomezia, Rome, Italy

    Ashraf Virmani, Luigi Pinto, Otto Bauermann & Andreas Diedenhofen

  3. Neurophysiology Laboratory, National Center for Toxicological Research, FDA, Jefferson, AR, 72079, USA

    Zbigniew K. Binienda

  4. Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, FDA, Jefferson, AR, 72079, USA

    Syed F. Ali

  5. Van Hall Larenstein and NHL University of Applied Sciences Agora 1, Postbus 1528, 8901BV, Leeuwarden, The Netherlands

    Feike R. van der Leij

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  1. Ashraf Virmani
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Virmani, A., Pinto, L., Bauermann, O. et al. The Carnitine Palmitoyl Transferase (CPT) System and Possible Relevance for Neuropsychiatric and Neurological Conditions. Mol Neurobiol 52, 826–836 (2015). https://doi.org/10.1007/s12035-015-9238-7

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