阿尔茨海默病和帕金森病杂志

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Neuronal Carnitine Palmitoyl Transferase1c in the Central Nervous System: Current Visions and Perspectives

Ashraf Virmani*,Luigi Pinto,Otto Bauermann,Saf Zerelli,Zbigniew Binienda,Syed Ali,Feike R van der Leij

The Carnitine Palmitoyl Transferase (CPT) system comprises several metabolically important enzymes of the carnitine/choline acyl transferase family. CPTs are transferases that allow the energy-neutral replacement of coenzyme A (CoA) by L-carnitine, and vice versa, when bound to acyl chains as (thio) esters. Together with acyl- CoA synthases and a carnitine/acyl carnitine translocase, the mitochondrial beta-oxidation of long-chain fatty acids is facilitated by distinct CPT proteins. CPT deficiencies manifest as disorders of mitochondrial fatty acid oxidation. Recently a new CPT isoform, CPT1c has been described which is found in entusiasmòc reticulum (ER) of neurons. Unlike CPT1a and CPT1b it has lower palmitoyl transferase activity. It is localised mainly in hypothalamus, amygdala and hippocampus, i.e., brain regions with roles in the control of food intake. It plays a role in energy homeostasis but its exact role in physiology of neurons is still not clear. Studies suggest a biosynthetic rather than catabolic role in long chain acyl carnitine production. The role of CPT1c may extend beyond simply the interchange of CoA and L-carnitine to acyl groups. Studies show that in the CNS the CPT1c affects ceramide levels, endocannabionoids and oxidative processes, and may play an important role in various brain functions such as learning. It is a player in insulin resistance that may occur as a result of oxidative damage and in altered redox status diseases such as metabolic cognitive syndrome, type 2 diabetes, neurodegenerative diseases and cancer. Unhealthy lifestyles, especially high sugar and fat diet in combination with other genetic and environmental risk factors, probably compromise metabolism at various levels. At the cellular level there would be increased ER stress as well as mitochondrial dysfunction leading to impaired oxidative phosphorylation and increased reliance on glucose (Warburg effect). Targeting CPT1c may provide insight on treatment of many metabolically-related diseases as well as pervasive developmental disorders.