Tremendous research efforts have been made regarding the pathogenesis of Parkinson’s disease(PD).However,there are still no effective strategies to restore midbrain dopaminergic(mDA)innervation and prevent disease pr...Tremendous research efforts have been made regarding the pathogenesis of Parkinson’s disease(PD).However,there are still no effective strategies to restore midbrain dopaminergic(mDA)innervation and prevent disease progression.One possibility is that we may have been neglecting the role of axons in mDA neuronal degeneration.This review first summarizes mDA axon development during the early stage of PD and discusses how axon guidance defects contribute to PD vulnerability.Furthermore,we review axonal transport dysregulation in the numerous PD-related genetic mutations,including Parkin,PINK1,DJ1,LRRK2 and SNCA.The evidence suggests that proper axonal transport is crucial for neuronal function and survival.Finally,advanced tools for axonal studies were evaluated,including light-sheet and super-resolution microscopy.These adapted microscopes have been used to help solve questions unanswered before.Overall,the role of axon terminals in the initiation of the degeneration cascade remains undeciphered,and more research in the related area may be conducted further to restore dopamine levels in the striatum to alleviate the motor complications of PD.展开更多
基金supported by funding from the Key Research and Development Program of Sichuan(2021YFS0382 to CX)the Medical Research Project of Jiangsu Commission of Health(M2022004 to CWL)+2 种基金Huai'an Natural Science Research Program(HAB202239 to CWL)the National Natural Science Foundation of China(General Program)(82271524 to LWD)the National Natural Science Foundation of China(Key Program)(32220103006 to LWD).
文摘Tremendous research efforts have been made regarding the pathogenesis of Parkinson’s disease(PD).However,there are still no effective strategies to restore midbrain dopaminergic(mDA)innervation and prevent disease progression.One possibility is that we may have been neglecting the role of axons in mDA neuronal degeneration.This review first summarizes mDA axon development during the early stage of PD and discusses how axon guidance defects contribute to PD vulnerability.Furthermore,we review axonal transport dysregulation in the numerous PD-related genetic mutations,including Parkin,PINK1,DJ1,LRRK2 and SNCA.The evidence suggests that proper axonal transport is crucial for neuronal function and survival.Finally,advanced tools for axonal studies were evaluated,including light-sheet and super-resolution microscopy.These adapted microscopes have been used to help solve questions unanswered before.Overall,the role of axon terminals in the initiation of the degeneration cascade remains undeciphered,and more research in the related area may be conducted further to restore dopamine levels in the striatum to alleviate the motor complications of PD.
