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Publication : Sulforaphene, a CDK5 Inhibitor, attenuates cognitive deficits in a transgenic mouse model of Alzheimer's disease via reducing Aβ Deposition, tau hyperphosphorylation and synaptic dysfunction.

First Author  Yang W Year  2023
Journal  Int Immunopharmacol Volume  114
Pages  109504 PubMed ID  36508924
Mgi Jnum  J:334392 Mgi Id  MGI:7424567
Doi  10.1016/j.intimp.2022.109504 Citation  Yang W, et al. (2023) Sulforaphene, a CDK5 Inhibitor, attenuates cognitive deficits in a transgenic mouse model of Alzheimer's disease via reducing Abeta Deposition, tau hyperphosphorylation and synaptic dysfunction. Int Immunopharmacol 114:109504
abstractText  BACKGROUND: Alzheimer's disease (AD) is the most common form of neurodegenerative disorder characterized by progressive loss of memory and cognitive functions. There are two pathological hallmarks, including accumulation of amyloid plaques composed of beta-amyloid peptide (Abeta) and deposits of neurofibrillatory tangles (NFT). Cyclin-dependent kinase 5 (CDK5), a serine/threonine kinase, plays an important role in synaptic plasticity and cognitive behavior. Sulforaphene (SF) has been demonstrated to exert anti-AD activity in AD rat model. In this study, we aimed to evaluate the cognitive deficits improving effects of SF on in TgCRND8 mice and to elucidate the underlying molecular mechanisms. METHODS: TgCRND8 mice were intragastrically treated with SF (25 and 50 mg/kg) for 4 months from 3-month-old. The cognitive functions were assessed using Morris Water Maze Test. Cultured primary mouse neurons were pre-treated with SF, followed by co-treatment with Abeta1-42 oligomers. CDK5 inhibitor (roscovitine) was used to determine the involvement of CDK5/p25 pathway in the anti-AD effects of SF in primary neurons. RESULTS: Our results showed that SF treatment significantly ameliorated the cognitive deficits in TgCRND8 mice and protected primary mouse neurons against Abeta1-42 induced neurotoxicity. SF could modulate the expression of Abeta production related markers, and suppress the phosphorylation of tau protein at specific sites in the TgCRND8 mice. In addition, SF enhanced the expressions of synaptic plasticity related markers and CDK5. SF also markedly suppressed the CDK5/p25 activity. CONCLUSIONS: SF is a potent CDK5 inhibitor and a potential therapeutic agent for treatment and prevention of AD. Moreover, SF inhibited the overexpression of CDK5 in primary neurons of mouse.
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