Molecular Neurobiology

, Volume 38, Issue 2, pp 146–152 | Cite as

In the Rat Brain Acetyl-l-carnitine Treatment Modulates the Expression of Genes Involved in Neuronal Ceroid Lipofuscinosis

  • Giovanna Traina
  • Rodolfo Bernardi
  • Enrico Cataldo
  • Monica Macchi
  • Mauro Durante
  • Marcello Brunelli


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.


Neuronal ceroid lipofuscinosis Suppression subtractive hybridization Lysosomal storage disorders Acetyl-l-carnitine Rat 



The authors thank Sigma-Tau Laboratories, Pomezia, Roma, for providing us with acetyl-l-carnitine and for partially supporting the work.


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Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Giovanna Traina
    • 1
  • Rodolfo Bernardi
    • 2
  • Enrico Cataldo
    • 3
  • Monica Macchi
    • 3
  • Mauro Durante
    • 2
  • Marcello Brunelli
    • 3
  1. 1.Department of Internal MedicineUniversity of PerugiaPerugiaItaly
  2. 2.Department of Agricultural Plant Biology, Genetic SectionUniversity of PisaPisaItaly
  3. 3.Department of Biology, General Physiology UnitUniversity of PisaPisaItaly

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