Abstract:
:Recently, the potent cholinesterase inhibitor (-)-huperzine A (HupA) was demonstrated to protect neuronal and glial cells against the cytotoxicity of beta-amyloid (Abeta). Since the unnatural (+)-HupA is a much less potent inhibitor, it was of interest to examine the stereoselectivity of cellular protection by the two isomers. In the present study, effects of (+)- and (-)-HupA on Abeta(25-35)-induced injury were compared in PC12 and NG108-15 neuroblastoma cell lines. Following a 24 h exposure to 1 microM Abeta(25-35), cell survival was markedly reduced, but preincubation with (+)-HupA or (-)-HupA (0.1-10 microM) enhanced survival significantly. The potency of (-)-HupA and (+)-HupA in protecting against Abeta toxicity was similar. This result contrasted with the stereoselectivity of cholinesterase inhibition in vitro and in vivo, in which (-)-HupA is about 50-fold more potent than (+)-HupA. It is concluded that the neuroprotective properties of HupA enantiomers have no relation to anti-cholinesterase activity.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Zhang HY,Liang YQ,Tang XC,He XC,Bai DLdoi
10.1016/s0304-3940(01)02437-5keywords:
subject
Has Abstractpub_date
2002-01-14 00:00:00pages
143-6issue
3eissn
0304-3940issn
1872-7972pii
S0304394001024375journal_volume
317pub_type
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