Neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's diseases have multifaceted nature because of the different factors contributing to their progression. The complex nature of neur...Neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's diseases have multifaceted nature because of the different factors contributing to their progression. The complex nature of neurodegenerative diseases has developed a pressing need to design multitarget-directed ligands to address the complementary pathways involved in these diseases. The major enzyme targets for development of therapeutics for Alzheimer's disease are cholinesterase and β-secretase enzymes. In this review, we discuss recent advances in profiling single target inhibitors based on these enzymes to multitarget-directed ligands as potential therapeutics for this devastating disease. In addition, therapeutics based on iron chelation strategy are discussed as well.展开更多
Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.T...Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.Therefore,the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated.In this review,we analyzed the challenges and critical points of the current anti-Aβtherapeutic strategies.In addition to Aβ,multiple pathological events such as tau hyperphosphorylation,oxidative stress,and neuroinflammation,which are involved in AD pathogenesis and synergistically drive disease progression,could be important targets for AD treatment.Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis.Systemic perspective addressing the disease pathogenesis within and outside the brain,as well as the multidomain intervention targeting risk factors and comorbidities,are important approaches for the therapeutic solutions of AD.展开更多
文摘Neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's diseases have multifaceted nature because of the different factors contributing to their progression. The complex nature of neurodegenerative diseases has developed a pressing need to design multitarget-directed ligands to address the complementary pathways involved in these diseases. The major enzyme targets for development of therapeutics for Alzheimer's disease are cholinesterase and β-secretase enzymes. In this review, we discuss recent advances in profiling single target inhibitors based on these enzymes to multitarget-directed ligands as potential therapeutics for this devastating disease. In addition, therapeutics based on iron chelation strategy are discussed as well.
基金supported by the National Natural Science Foundation of China(91749206,81930028,81625007,81870860,31921003)。
文摘Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.Therefore,the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated.In this review,we analyzed the challenges and critical points of the current anti-Aβtherapeutic strategies.In addition to Aβ,multiple pathological events such as tau hyperphosphorylation,oxidative stress,and neuroinflammation,which are involved in AD pathogenesis and synergistically drive disease progression,could be important targets for AD treatment.Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis.Systemic perspective addressing the disease pathogenesis within and outside the brain,as well as the multidomain intervention targeting risk factors and comorbidities,are important approaches for the therapeutic solutions of AD.
