Natural antioxidants in Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by severe cognitive impairment that ultimately leads to death. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists to the NMDA receptors. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. In the past several years, based on in vitro and in vivo studies in laboratory animals, natural antioxidants, such as resveratrol, curcumin and acetyl-L-carnitine have been proposed as alternative therapeutic agents for AD. An increasing number of studies demonstrated the efficacy of primary antioxidants, such as polyphenols, or secondary antioxidants, such as acetylcarnitine, to reduce or to block neuronal death occurring in the pathophysiology of this disorder. These studies revealed that other mechanisms than the antioxidant activities could be involved in the neuroprotective effect of these compounds. This paper discusses the evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms leading to the upregulation of vitagenes. Furthermore, future development of novel antioxidant drugs targeted to the mitochondria should result in effectively slowing disease progression. The association with new drug delivery systems may be desirable and useful for the therapeutic use of antioxidants in human neurodegenerative diseases.
Mancuso
Cesare
C
Catholic University School of Medicine, Institute of Pharmacology, Largo F Vito, 00168 Roma, Italy.
Bates
Timothy E
TE
Butterfield
D Allan
DA
Calafato
Stella
S
Cornelius
Carolin
C
De Lorenzo
Antonino
A
Dinkova Kostova
Albena T
AT
Calabrese
Vittorio
V
D000108:Acetylcarnitine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D013267:Stilbenes; D000108:Acetylcarnitine; D000077185:Resveratrol