CaMKIIα Signaling Is Required for the Neuroprotective Effects of Dl-3-n-Butylphthalide in Alzheimer's Disease.
Bing-Qiu LiLing-Zhi XuFang-Yu LiYing LiYu ZhaoHeng ZhangMei-Na QuanJian-Ping JiaPublished in: Molecular neurobiology (2022)
Alzheimer's disease (AD) is the most common form of neurodegenerative disease and most anti-AD drugs have failed in clinical trials; hence, it is urgent to find potentially effective drugs against AD. DL-3-n-butylphthalide (NBP) is a compound extracted from celery seed and is a multiple-target drug. Several studies have demonstrated the neuroprotective effects of NBP on cognitive impairment, but the mechanisms of NBP remains relatively unexplored. In this study, we found that NBP could alleviated the increase of intracellular Ca 2+ and reversed down-regulation of Ca 2+ /calmodulin-dependent protein kinase alpha (CaMKIIα) signaling and rescued neuronal apoptosis in SH-SY5Y cells treated by Aβ oligomers. However, these neuroprotective effects of NBP on neuronal damage and CaMKIIα signaling were abolished when CaMKIIα expression was knocked down or its activity was inhibited. Thus, our findings suggested that CaMKIIα signaling was required for the neuroprotective effects of NBP in AD and provided an improved basis for elucidating the mechanism and treatment of NBP in AD.
Keyphrases
- cerebral ischemia
- protein kinase
- clinical trial
- cell cycle arrest
- cognitive impairment
- oxidative stress
- induced apoptosis
- poor prognosis
- cognitive decline
- cell death
- endoplasmic reticulum stress
- randomized controlled trial
- emergency department
- brain injury
- blood brain barrier
- long non coding rna
- signaling pathway
- reactive oxygen species
- open label
- pi k akt
- electronic health record
- mild cognitive impairment