Neurodegenerative diseases(e.g.,Alzheimer's,Parkinson's,Huntington's disease,and Amyotrophic Lateral Sclerosis)are major health threats for the aging population and their prevalences continue to rise with ...Neurodegenerative diseases(e.g.,Alzheimer's,Parkinson's,Huntington's disease,and Amyotrophic Lateral Sclerosis)are major health threats for the aging population and their prevalences continue to rise with the increasing of life expectancy.Although progress has been made,there is still a lack of effective cures to date,and an in-depth understanding of the molecular and cellular mechanisms of these neurodegenerative diseases is imperative for drug development.Protein phosphorylation,regulated by protein kinases and protein phosphatases,participates in most cellular events,whereas aberrant phosphorylation manifests as a main cause of diseases.As evidenced by pharmacological and pathological studies,protein kinases are proven to be promising therapeutic targets for various diseases,such as cancers,central nervous system disorders,and cardiovascular diseases.The mechanisms of protein phosphatases in pathophysiology have been extensively reviewed,but a systematic summary of the role of protein kinases in the nervous system is lacking.Here,we focus on the involvement of protein kinases in neurodegenerative diseases,by summarizing the current knowledge on the major kinases and related regulatory signal transduction pathways implicated in diseases.We further discuss the role and complexity of kinase-kinase networks in the pathogenesis of neurodegenerative diseases,illustrate the advances of clinical applications of protein kinase inhibitors or novel kinase-targeted therapeutic strategies(such as antisense oligonucleotides and gene therapy)for effective prevention and early intervention.展开更多
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0507200)National Natural Science Foundation of China(32070961)+2 种基金Natural Science Foundation of Sichuan Province(2024NSFSC1643)Sichuan University Postdoctoral Interdisciplinary Innovation Fund(JCXK2206)Postdoctoral Research Program of West China Hospital,Sichuan University(2023HXBH126).
文摘Neurodegenerative diseases(e.g.,Alzheimer's,Parkinson's,Huntington's disease,and Amyotrophic Lateral Sclerosis)are major health threats for the aging population and their prevalences continue to rise with the increasing of life expectancy.Although progress has been made,there is still a lack of effective cures to date,and an in-depth understanding of the molecular and cellular mechanisms of these neurodegenerative diseases is imperative for drug development.Protein phosphorylation,regulated by protein kinases and protein phosphatases,participates in most cellular events,whereas aberrant phosphorylation manifests as a main cause of diseases.As evidenced by pharmacological and pathological studies,protein kinases are proven to be promising therapeutic targets for various diseases,such as cancers,central nervous system disorders,and cardiovascular diseases.The mechanisms of protein phosphatases in pathophysiology have been extensively reviewed,but a systematic summary of the role of protein kinases in the nervous system is lacking.Here,we focus on the involvement of protein kinases in neurodegenerative diseases,by summarizing the current knowledge on the major kinases and related regulatory signal transduction pathways implicated in diseases.We further discuss the role and complexity of kinase-kinase networks in the pathogenesis of neurodegenerative diseases,illustrate the advances of clinical applications of protein kinase inhibitors or novel kinase-targeted therapeutic strategies(such as antisense oligonucleotides and gene therapy)for effective prevention and early intervention.
