Accumulation of amyloid-βpeptide(Aβ)is a key hallmark of Alzheimer’s disease(AD).A retinamide–platinum complex(RP)consisting of an Aβ-binding group,[Pt(bipyridine)Cl]+,and a derivative of neurotrophic retinoic ac...Accumulation of amyloid-βpeptide(Aβ)is a key hallmark of Alzheimer’s disease(AD).A retinamide–platinum complex(RP)consisting of an Aβ-binding group,[Pt(bipyridine)Cl]+,and a derivative of neurotrophic retinoic acid was designed to diminish the neurotoxicity associated with Aβaggregates and to quell the Aβ-induced neuroinflammation.RP remarkably inhibited the self-and metal-induced Aβaggregation,reduced the production of reactive oxygen species,lowered the neurotoxicity of Aβaggregates,and protected the plasma membrane of neural cells.The RP–Aβconjugates are readily phagocytosed and degraded by microglial cells,thus preventing them from polarizing into the inflammatory M1 phenotype and secreting proinflammatory cytokines.Moreover,RP alleviated the behavioral dysfunction and paralysis of Aβ-transgenic C.elegans.The results demonstrate that RP is a potential nontoxic anti-AD agent capable of inhibiting Aβaggregation and protecting nerve cells simultaneously.The dual action of RP expands the application range of platinum complexes and the structural types of anti-Alzheimer’s drugs.展开更多
基金the National Natural Science Foundation of China(Grants 22577051 and 21877059).
文摘Accumulation of amyloid-βpeptide(Aβ)is a key hallmark of Alzheimer’s disease(AD).A retinamide–platinum complex(RP)consisting of an Aβ-binding group,[Pt(bipyridine)Cl]+,and a derivative of neurotrophic retinoic acid was designed to diminish the neurotoxicity associated with Aβaggregates and to quell the Aβ-induced neuroinflammation.RP remarkably inhibited the self-and metal-induced Aβaggregation,reduced the production of reactive oxygen species,lowered the neurotoxicity of Aβaggregates,and protected the plasma membrane of neural cells.The RP–Aβconjugates are readily phagocytosed and degraded by microglial cells,thus preventing them from polarizing into the inflammatory M1 phenotype and secreting proinflammatory cytokines.Moreover,RP alleviated the behavioral dysfunction and paralysis of Aβ-transgenic C.elegans.The results demonstrate that RP is a potential nontoxic anti-AD agent capable of inhibiting Aβaggregation and protecting nerve cells simultaneously.The dual action of RP expands the application range of platinum complexes and the structural types of anti-Alzheimer’s drugs.
