Biphasic effects of statins on neuron cell functions under oxygen-glucose deprivation and normal culturing conditions via different mechanisms

Abstract While there is a growing interest in the use of statins, HMG‐CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically...

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Main Authors: Hui Wang (Author), Yun Chen (Author), Ping Li (Author), Yan Chen (Author), Danfang Yu (Author), Qian Tan (Author), Xiaoli Liu (Author), Zhenli Guo (Author)
Format: Book
Published: Wiley, 2022-10-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Hui Wang  |e author 
700 1 0 |a Yun Chen  |e author 
700 1 0 |a Ping Li  |e author 
700 1 0 |a Yan Chen  |e author 
700 1 0 |a Danfang Yu  |e author 
700 1 0 |a Qian Tan  |e author 
700 1 0 |a Xiaoli Liu  |e author 
700 1 0 |a Zhenli Guo  |e author 
245 0 0 |a Biphasic effects of statins on neuron cell functions under oxygen-glucose deprivation and normal culturing conditions via different mechanisms 
260 |b Wiley,   |c 2022-10-01T00:00:00Z. 
500 |a 2052-1707 
500 |a 10.1002/prp2.1001 
520 |a Abstract While there is a growing interest in the use of statins, HMG‐CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury‐induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation‐independent manner. Other mechanisms are involved in the pro‐apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS. 
546 |a EN 
690 |a neuron cells 
690 |a OGD 
690 |a oxidative stress 
690 |a prenylation 
690 |a statins 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Pharmacology Research & Perspectives, Vol 10, Iss 5, Pp n/a-n/a (2022) 
787 0 |n https://doi.org/10.1002/prp2.1001 
787 0 |n https://doaj.org/toc/2052-1707 
856 4 1 |u https://doaj.org/article/24e020ae988b4ce9a0f87b5749a3da4d  |z Connect to this object online.