Progressive noradrenergic degeneration and motor cortical dysfunction in Parkinson’s disease  

作　　者：Wei Zhou Hong-Yuan Chu 

机构地区：[1]Department of Pharmacology and Physiology,Georgetown University Medical Center,Washington D.C.,WA,20007,USA [2]Aligning Science Across Parkinson’s(ASAP)Collaborative Research Network,Chevy Chase,MD,20852,USA

出　　处：《Acta Pharmacologica Sinica》2025年第4期829-835,共7页中国药理学报(英文版)

基　　金：funded in part by Aligning Science Across Parkinson’s(ASAP-020572);NIH grants(R01NS121371 and R21NS135545);Department of Defense Congressionally Directed Medical Research Programs(W81XWH-21-1-0943);Parkinson’s Foundation(PF-IMP-1045313).

摘　　要：The locus coeruleus norepinephrine(LC-NE)system plays an important role in regulating brain function,and its neuronal loss has been well-documented in Parkinson’s disease(PD).The LC-NE neurodegeneration is believed to underlie various nonmotor symptoms in people with PD,including neuropsychiatric deficits,sleep disruptions,and cognitive impairments.Of particular interest,LC-NE neurons send intensive axonal projections to the motor regions of the cerebral cortex.However,how NE depletion in the motor cortex contributes to PD pathophysiology remains poorly understood.In addition,recent studies provided increasing mechanistic insights into secondary changes in the cerebral cortex as LC-NE degenerates,which might involve its interaction with dopaminergic signaling during the chronic course of the disease.In the present article,we briefly discuss clinical and preclinical studies that support the critical roles of LC-NE neurodegeneration and motor cortical dysfunction in both motor and nonmotor deficits in Parkinsonian states.We focus our discussion on the potential impact of LC-NE neurodegeneration on motor cortical function and the subsequent symptom manifestation.Last,we propose future research directions that can advance our understanding of cortical pathophysiology in PD by integrating noradrenergic degeneration.

关 键 词：locus coeruleus NOREPINEPHRINE DOPAMINE parkinson’s disease motor cortex cognition 

分 类 号：R742.5[医药卫生—神经病学与精神病学]