title: In the rat brain acetyl-L-carnitine treatment modulates the expression of genes involved in neuronal ceroid lipofuscinosis.
abstract: Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supraphysiological concentration, is neuroprotective. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. Suppression subtractive hybridization methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after ALC treatment. The method generates an equalized representation of differentially expressed genes irrespective of their relative abundance and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes which are regulated by ALC. We report that ALC treatment: (1) upregulates lysosomal H(+)/ATPase gene expression and (2) downregulates myelin basic protein gene expression. The expression of these genes is altered in some forms of neuronal ceroid lipofuscinosis (NCL) pathologies. In this case, ALC might rebalance the disorders underlying NCL disease represented by a disturbance in pH homeostasis affecting the acidification of vesicles transported to lysosomal compartment for degradation. This study provides evidence that ALC controls genes involved in these serious neurological pathologies and provides insights into the ways in which ALC might exert its therapeutic benefits.
authors: Department of Internal Medicine, University of Perugia, Via San Costanzo, 06126 Perugia, Italy. traina@unipg.it
authors: Giovanna
authors: G
authors: Traina
authors: Rodolfo
authors: R
authors: Bernardi
authors: Enrico
authors: E
authors: Cataldo
authors: Monica
authors: M
authors: Macchi
authors: Mauro
authors: M
authors: Durante
authors: Marcello
authors: M
authors: Brunelli
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism
chemical_list: D004676:Myelin Basic Protein; D018697:Nootropic Agents; D021122:Protein Subunits; D000108:Acetylcarnitine; D025262:Vacuolar Proton-Translocating ATPases