NRBF2 has been identified as the fifth component of PI3KC3 complex and is required for maintaining the kinase activity to promote autophagy.However,the physiological and pathological roles of NRBF2are largely unknown.
Alzheimer's disease(AD)is a prevalent and deleterious neurodegenerative disorder characterized by an irreversible and progressive impairment of cognitive abilities as well as the formation of amyloidβ(Aβ)plaques...Alzheimer's disease(AD)is a prevalent and deleterious neurodegenerative disorder characterized by an irreversible and progressive impairment of cognitive abilities as well as the formation of amyloidβ(Aβ)plaques and neurofibrillary tangles(NFTs)in the brain.By far,the precise mechanisms of AD are not fully understood and no interventions are available to effectively slow down progression of the disease.Autophagy is a conserved degradation pathway that is crucial to maintain cellular homeostasis by targeting damaged organelles,pathogens,and disease-prone protein aggregates to lysosome for degradation.Emerging evidence suggests dysfunctional autophagy clearance pathway as a potential cellular mechanism underlying the pathogenesis of AD in affected neurons.Here we summarize the current evidence for autophagy dysfunction in the pathophysiology of AD and discuss the role of autophagy in the regulation of AD-related protein degradation and neuroinflammation in neurons and glial cells.Finally,we review the autophagy modulators reported in the treatment of AD models and discuss the obstacles and opportunities for potential clinical application of the novel autophagy activators for AD therapy.展开更多
基金supported by the China Ministry of Science and Technology grant(No.Mo ST-2017YFE0120100)The Science and Technology Development Fund,Macao SAR(Nos.024/2017/AMJ,0128/2019/A3)+2 种基金the University of Macao grant(NoMYRG2019-00129-ICMS)(to JHL)supported by GRF/HKBU(Nos.12101417,12100618)HMRF(Nos.17182541,17182551)(to ML)。
文摘NRBF2 has been identified as the fifth component of PI3KC3 complex and is required for maintaining the kinase activity to promote autophagy.However,the physiological and pathological roles of NRBF2are largely unknown.
基金This study was supported by China minister of Science and Technology grant MoST-2017YFE0120100the Science and Technology Development Fund,Macao SAR(No.0110/2018/A3,0128/2019/A3,China)+1 种基金the University of Macao grants(No.MYRG2019-00129-ICMS,China)awarded to Jia-Hong LuNIH/R01NS060123 and R01 R01AG072520(USA)awarded to Zhenyu Yue.
文摘Alzheimer's disease(AD)is a prevalent and deleterious neurodegenerative disorder characterized by an irreversible and progressive impairment of cognitive abilities as well as the formation of amyloidβ(Aβ)plaques and neurofibrillary tangles(NFTs)in the brain.By far,the precise mechanisms of AD are not fully understood and no interventions are available to effectively slow down progression of the disease.Autophagy is a conserved degradation pathway that is crucial to maintain cellular homeostasis by targeting damaged organelles,pathogens,and disease-prone protein aggregates to lysosome for degradation.Emerging evidence suggests dysfunctional autophagy clearance pathway as a potential cellular mechanism underlying the pathogenesis of AD in affected neurons.Here we summarize the current evidence for autophagy dysfunction in the pathophysiology of AD and discuss the role of autophagy in the regulation of AD-related protein degradation and neuroinflammation in neurons and glial cells.Finally,we review the autophagy modulators reported in the treatment of AD models and discuss the obstacles and opportunities for potential clinical application of the novel autophagy activators for AD therapy.
