α-Tocotrienol Protects Neurons by Preventing Tau Hyperphosphorylation via Inhibiting Microtubule Affinity-Regulating Kinase Activation.
Yuhong LiuYunxi ChenKoji FukuiPublished in: International journal of molecular sciences (2024)
In the pathological process of Alzheimer's disease, neuronal cell death is closely related to the accumulation of reactive oxygen species. Our previous studies have found that oxidative stress can activate microtubule affinity-regulating kinases, resulting in elevated phosphorylation levels of tau protein specifically at the Ser262 residue in N1E-115 cells that have been subjected to exposure to hydrogen peroxide. This process may be one of the pathogenic mechanisms of Alzheimer's disease. Vitamin E is a fat-soluble, naturally occurring antioxidant that plays a crucial role in biological systems. This study aimed to examine the probable processes that contribute to the inhibiting effect on the abnormal phosphorylation of tau protein and the neuroprotective activity of a particular type of vitamin E, α-tocotrienol. The experimental analysis revealed that α-tocotrienol showed significant neuroprotective effects in the N1E-115 cell line. Our data further suggest that one of the mechanisms underlying the neuroprotective effects of α-tocotrienol may be through the inhibition of microtubule affinity-regulated kinase activation, which significantly reduces the oxidative stress-induced aberrant elevation of p-Tau (Ser262) levels. These results indicate that α-tocotrienol may represent an intriguing strategy for treating or preventing Alzheimer's disease.
Keyphrases
- hydrogen peroxide
- oxidative stress
- cell death
- cerebrospinal fluid
- protein kinase
- cognitive decline
- reactive oxygen species
- induced apoptosis
- cerebral ischemia
- cell cycle arrest
- nitric oxide
- amino acid
- adipose tissue
- spinal cord
- protein protein
- transcription factor
- small molecule
- single cell
- electronic health record
- subarachnoid hemorrhage
- spinal cord injury
- big data
- mild cognitive impairment
- pi k akt
- heat shock protein
- anti inflammatory