ATP-Sensitive K+ Channel in Nigra Dopamine Neurons is a Novel Target for Tetrahydroprotoberberines` Neuroprotection
Pp. 3-18 (16)
Kechun Yang, Devin H. Taylor and Jie Wu
Tetrahydroprotoberberines (THPBs), active ingredients of a Chinese
medicinal herb, are a series of compounds, mainly comprised of l-stepholidine (l-SPD),
l-tetrahydropalmatine (l-THP), and tetrahydroberberine (THB). These compounds have
been reported to target at dopamine (DA) receptors in both the nigrostriatal and
mesocorticolimbic dopaminergic (DAergic) pathways, and may have a role in
modulation of DA-associated diseases . Recent studies have shown that the THPBs
slow down the progression of neuronal degeneration in the substantia nigra compacta
(SNc) of Parkinson disease (PD) patients and animal models of PD, while coadministration
of THPBs and levodopa significantly reduces the motor symptoms of PD
patients. Our recent new findings indicate that targeting at ATP-sensitive K+ (KATP)
channels in SNc DA neurons can be a novel mechanism underlying THPBs’
neuroprotective effects. Therefore, THPBs might exhibit novel therapeutic potential for
treatment of PD.
Dopamine neuron, hydrogen peroxide, KATP channel, neuroprotection,
Parkinson’s disease, substantia nigra, tetrahydroprotoberberine.
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.