The roles and mechanisms of axon guidance molecules in alpha-synuclein-related neurodegenerative diseases

Zhang Yingbi; Li Minghui; Zhang Xiaorui; Yin Jihong; Wang Peng

doi:10.12307/2026.083

Abstract：BACKGROUND:Axon guidance molecules may play a critical role in alpha-synuclein-related neurodegenerative diseases. OBJECTIVE:To explore the roles and mechanisms of axon guidance molecules in alpha-synuclein-related neurodegenerative diseases. METHODS:The first author conducted a comprehensive search of databases including CNKI,WanFang Data,PubMed,Nature,Embase,Web of Science,JAMA,and BMJ.We systematically collected and organized literature on axon guidance factors and α-synuclein-related neurodegenerative diseases in recent years.The search terms were"Parkinson's disease,axon guidance molecules,dementia with Lewy bodies,multiple system atrophy,pure autonomic failure"in Chinese and"Parkinson's disease,axon guidance molecules,Netrin,Ephrin,Semaphorin,Slit,dementia with Lewy bodies,multiple system atrophy,pure autonomic failure"in English.After screening,89 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:The axon guidance factor protein family includes Netrins,Ephrins,Semaphorins,and Slits.Netrins modulate the activity of dopaminergic neurons by influencing intestinal factors and through DCC receptors,thereby impacting the progression of neurodegenerative diseases.Within the Ephrins family,EphrinA/EphA is involved in mediating neuronal regeneration signals.EphA1 regulates inflammation and neuropathology via the CXC chemokine ligand 12/CXC chemokine receptor 4 pathway,affecting disease development.Semaphorins-3 within the Semaphorins family can improve behavioral symptoms of neurodegenerative diseases by guiding the growth of axons from the substantia nigra to the striatum in dopaminergic neurons.On the axonal conduction pathway of dopaminergic neurons,Slits regulate the localization and pathfinding process through the Slit-Robo signaling,ensuring the accuracy of neuronal signal transmission pathways,which is crucial for maintaining and repairing neuronal connections.