Selenoproteins are a family of special proteins that contain the 21st amino acid, selenocysteine (Sec), in their sequence. Selenoprotein P has 10 Sec residues and modulates selenium homeostasis and redox balance in the brain. Previously, we found that the Sec-devoid His-rich motif of selenoprotein P (Selenop-H) suppressed metal-induced aggregation and neurotoxicities of both Aβ and tau in vitro. To investigate the intervening capacity of Selenop-H on the neuropathology and cognitive deficits of triple transgenic AD (3 × Tg-AD) mice, the Selenop-H gene packaged in rAAV9 was delivered into the hippocampal CA3 regions of mice via stereotaxic injection. Four months later, we demonstrated that Selenop-H (1) improved the spatial learning and memory deficits, (2) alleviated neuron damage and synaptic protein loss, (3) inhibited both tau pathology and amyloid beta protein (Aβ) aggregation, (4) activated both BDNF- and Src-mediated TrkB signaling, and (5) increased MT3 and ZnT3 levels and restored Zn2+ homeostasis in the mice model of AD. The study revealed that Selenop-H is potent in ameliorating AD-related neuropathology and cognitive deficits by modulating TrkB signaling and Zn2+ homeostasis.
Keyphrases
- amino acid
- high fat diet induced
- heavy metals
- traumatic brain injury
- wild type
- insulin resistance
- oxidative stress
- cerebrospinal fluid
- white matter
- protein protein
- mouse model
- cognitive decline
- genome wide
- risk assessment
- single cell
- high glucose
- small molecule
- brain injury
- binding protein
- signaling pathway
- adipose tissue
- tyrosine kinase
- ultrasound guided
- functional connectivity
- resting state
- transcription factor
- stress induced
- subarachnoid hemorrhage
- dna methylation
- mild cognitive impairment
- prefrontal cortex