TY - JOUR
T1 - A novel thiol antioxidant that crosses the blood brain barrier protects dopaminergic neurons in experimental models of Parkinson's disease
AU - Bahat-Stroomza, Merav
AU - Gilgun-Sherki, Yossi
AU - Offen, Daniel
AU - Panet, Hana
AU - Saada, Ann
AU - Krool-Galron, Nili
AU - Barzilai, Aari
AU - Atlas, Daphne
AU - Melamed, Eldad
PY - 2005/2
Y1 - 2005/2
N2 - It is believed that oxidative stress (OS) plays an important role in the loss of dopaminergic nigrostriatal neurons in Parkinson's disease (PD) and that treatment with antioxidants might be neuroprotective. However, most currently available antioxidants cannot readily penetrate the blood brain barrier after systemic administration. We now report that AD4, the novel low molecular weight thiol antioxidant and the N-acytel cysteine (NAC) related compound, is capable of penetrating the brain and protects neurons in general and especially dopaminergic cells against various OS-generating neurotoxins in tissue cultures. Moreover, we found that treatment with AD4 markedly decreased the damage of dopaminergic neurons in three experimental models of PD. AD4 suppressed amphetamine-induced rotational behaviour in rats with unilateral 6-OHDA-induced nigral lesion. It attenuated the reduction in striatal dopamine levels in mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP). It also reduced the dopaminergic neuronal loss following chronic intrajugular administration of rotenone in rats. Our findings suggest that AD4 is a novel potential new neuroprotective drug that might be effective at slowing down nigral neuronal degeneration and illness progression in patients with PD.
AB - It is believed that oxidative stress (OS) plays an important role in the loss of dopaminergic nigrostriatal neurons in Parkinson's disease (PD) and that treatment with antioxidants might be neuroprotective. However, most currently available antioxidants cannot readily penetrate the blood brain barrier after systemic administration. We now report that AD4, the novel low molecular weight thiol antioxidant and the N-acytel cysteine (NAC) related compound, is capable of penetrating the brain and protects neurons in general and especially dopaminergic cells against various OS-generating neurotoxins in tissue cultures. Moreover, we found that treatment with AD4 markedly decreased the damage of dopaminergic neurons in three experimental models of PD. AD4 suppressed amphetamine-induced rotational behaviour in rats with unilateral 6-OHDA-induced nigral lesion. It attenuated the reduction in striatal dopamine levels in mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP). It also reduced the dopaminergic neuronal loss following chronic intrajugular administration of rotenone in rats. Our findings suggest that AD4 is a novel potential new neuroprotective drug that might be effective at slowing down nigral neuronal degeneration and illness progression in patients with PD.
KW - 6-OHDA
KW - AD4
KW - Antioxidants
KW - MPTP
KW - Oxidative stress
KW - Parkinson's disease
KW - Rotenone
UR - http://www.scopus.com/inward/record.url?scp=14944376569&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2005.03889.x
DO - 10.1111/j.1460-9568.2005.03889.x
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C2 - 15733082
AN - SCOPUS:14944376569
SN - 0953-816X
VL - 21
SP - 637
EP - 646
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 3
ER -