Acetyl-l-carnitine (ALC) has been shown to exhibit many neuromodulatory and neurotrophic actions on neuron activity. It is a molecule of considerable interest for its clinical application in various disorders, including Alzheimer’s disease and painful neuropathies. Studies reported that ALC treatment produces long lasting effects in learning processes, suggesting an involvement of gene modulation. The ALC action on gene expression is recently revealed by suppression subtractive hybridization method studies for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after ALC treatment of rats (Traina et al., Mol. Brain Res, 132, 57-63, 2004). The technique generates an equalized representation of differentially expressed genes and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes that are regulated after ALC treatment. We have singled out a multifocal control of ALC: i) an up-regulation of both 14, 3, 3 protein, gamma subunit, and of heat shock protein 72, contributing to establish a cytoprotective state in inflammation, neurodegenerative disorders, and aging; ii) a down-regulation of ATP-synthase lipid-binding protein, and positively increases lysosomal H+ATPase gene expression. The effects have implications in ceroid lipofuscinosis pathology. In addition, ALC treatment up-regulates VDAC1 gene expression that might exert an antiapoptotic role, and seems to have a pivotal role on synaptic plasticity (Traina et al., Neurochem. Int., in press). Finally, ALC down-regulates ferritin-H expression, and myelin basic protein, and up-regulates kinesin1 light chain, responsible for many of the microtubule-dependent transport pathways for fast anterograde axonal transport. It is associated with amyloid precursor proteins. Our data on gene expression, therefore, might be of relevant importance for a human treatment of many clinical malignancies.
Modulation of gene expression in the rat brain by acetyl-l-carnitine
BERNARDI, RODOLFO;
2006-01-01
Abstract
Acetyl-l-carnitine (ALC) has been shown to exhibit many neuromodulatory and neurotrophic actions on neuron activity. It is a molecule of considerable interest for its clinical application in various disorders, including Alzheimer’s disease and painful neuropathies. Studies reported that ALC treatment produces long lasting effects in learning processes, suggesting an involvement of gene modulation. The ALC action on gene expression is recently revealed by suppression subtractive hybridization method studies for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after ALC treatment of rats (Traina et al., Mol. Brain Res, 132, 57-63, 2004). The technique generates an equalized representation of differentially expressed genes and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes that are regulated after ALC treatment. We have singled out a multifocal control of ALC: i) an up-regulation of both 14, 3, 3 protein, gamma subunit, and of heat shock protein 72, contributing to establish a cytoprotective state in inflammation, neurodegenerative disorders, and aging; ii) a down-regulation of ATP-synthase lipid-binding protein, and positively increases lysosomal H+ATPase gene expression. The effects have implications in ceroid lipofuscinosis pathology. In addition, ALC treatment up-regulates VDAC1 gene expression that might exert an antiapoptotic role, and seems to have a pivotal role on synaptic plasticity (Traina et al., Neurochem. Int., in press). Finally, ALC down-regulates ferritin-H expression, and myelin basic protein, and up-regulates kinesin1 light chain, responsible for many of the microtubule-dependent transport pathways for fast anterograde axonal transport. It is associated with amyloid precursor proteins. Our data on gene expression, therefore, might be of relevant importance for a human treatment of many clinical malignancies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
