摘要
Parkinson's disease(PD)is a common neurological disorder that is defined by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta,eventually leading to striatal dopamine depletion.Resting tremors,rigid muscles,bradykinesia,and in rare circumstances,postural instability are symptoms of low dopamine levels.One to two percent of people over 65 worldwide is affected with PD,making it the second most common neurological illness in the world[1,2].Uncertainty about the cause and course of PD persists,as do the biological pathways that drive the disease[3].Mutations in the leucine-rich repeat kinase 2(LRRK2)gene are the most common cause of familial PD[4].LRRK2 missense mutations increase the risk of developing late-onset autosomal dominant PD,which is clinically comparable to sporadic PD[5,6].LRRK2 PD neuropathology is comparable to sporadic PD neuropathology,with LRRK2 patients experiencing progressive neurodegeneration of the nigrostriatal pathway,frequently resulting in alpha-Synuclein-positive Lewy bodies and brain tau pathology[5,7-9].While LRRK2 coding mutations are associated with sporadic PD,frequent non-coding variants at the LRRK2 locus are associated with an increased risk of developing PD[10-13].
