TY - JOUR
T1 - Natural antioxidants in Alzheimer's disease
AU - Mancuso, Cesare
AU - Bates, Timothy E.
AU - Butterfield, D. Allan
AU - Calafato, Stella
AU - Cornelius, Carolin
AU - De Lorenzo, Antonino
AU - Dinkova Kostova, Albena T.
AU - Calabrese, Vittorio
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - Acetyl-L-carnitine
KW - Alzheimer's disease
KW - Curcumin
KW - Haem oxygenase
KW - Heat-shock proteins
KW - Resveratrol
KW - Vitagenes
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UR - http://www.scopus.com/inward/citedby.url?scp=39549119848&partnerID=8YFLogxK
U2 - 10.1517/13543784.16.12.1921
DO - 10.1517/13543784.16.12.1921
M3 - Article
C2 - 18042001
AN - SCOPUS:39549119848
SN - 1354-3784
VL - 16
SP - 1921
EP - 1931
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 12
ER -