Acetyl-L-carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere.
Since ALCAR and L-carnitine are "shuttles" of long chain fatty acids between the cytosol and the mitochondria to undergo beta-oxidation, they play an essential role in energy production and in clearing toxic accumulations of fatty acids in the mitochondria. ALCAR has been considered of potential use in senile dementia of the Alzheimer type (SDAT) because of its ability to serve as a precursor for acetylcholine. However, pharmacological studies with ALCAR in animals have demonstrated its facility to maximize energy production and promote cellular membrane stability, particularly its ability to restore membranal changes that are age-related. Since recent investigations have implicated abnormal energy processing leading to cell death, and severity-dependent membrane disruption in the pathology of Alzheimer's disease, we speculate that the beneficial effects associated with ALCAR administration in Alzheimer patients are due not only to its cholinergic properties, but also to its ability to support physiological cellular functioning at the mitochondrial level. This hypothetical mechanism of action is discussed with respect to compelling supportive animal studies and recent observations of significant decrease of carnitine acetyltransferase (the catalyst of L-carnitine acylation to acetyl-L-carnitine) in autopsied Alzheimer brains.
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Sigma-Tau Pharmaceuticals, Department of Scientific Affairs, Gaithersburg, Maryland 20878.
Calvani
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Bravi
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Bhuachalla
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D000108:Acetylcarnitine / Q000494:pharmacology / Q000627:therapeutic use*; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000108:Acetylcarnitine; D002332:Carnitine O-Acetyltransferase