Noradrenaline in Alzheimer's Disease: A New Potential Therapeutic Target

被引:21
|
作者
Gutierrez, Irene L. [1 ]
Dello Russo, Cinzia [2 ,3 ]
Novellino, Fabiana [1 ,4 ]
Caso, Javier R. [1 ]
Garcia-Bueno, Borja [1 ]
Leza, Juan C. [1 ]
Madrigal, Jose L. M. [1 ]
机构
[1] Univ Complutense Madrid UCM, Sch Med, Dept Pharmacol & Toxicol,Ctr Invest Biomed Red Sa, Inst Invest Sanitaria Hosp 12 Octubre Imas12,Inst, Avda Complutense S-N, Madrid 28040, Spain
[2] Univ Cattolica Sacro Cuore, Fdn Policlin Univ A Gemelli IRCCS, Dept Healthcare Surveillance & Bioeth, Sect Pharmacol, I-00168 Rome, Italy
[3] Univ Liverpool, Inst Syst Mol & Integrat Biol ISMIB, Dept Pharmacol & Therapeut, Liverpool L69 3GL, Merseyside, England
[4] CNR, Inst Mol Bioimaging & Physiol IBFM, I-88100 Catanzaro, Italy
关键词
noradrenaline; norepinephrine; locus coeruleus; Alzheimer's disease; neuroinflammation; inflammation; cytokines; glia; NITRIC-OXIDE SYNTHASE; VAGUS NERVE-STIMULATION; ACTIVATED RECEPTOR-GAMMA; LOCUS-COERULEUS; COGNITIVE DEFICITS; PREFRONTAL CORTEX; MICROGLIAL CELLS; MOUSE MODEL; CLASS-II; NORADRENERGIC REGULATION;
D O I
10.3390/ijms23116143
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A growing body of evidence demonstrates the important role of the noradrenergic system in the pathogenesis of many neurodegenerative processes, especially Alzheimer's disease, due to its ability to control glial activation and chemokine production resulting in anti-inflammatory and neuroprotective effects. Noradrenaline involvement in this disease was first proposed after finding deficits of noradrenergic neurons in the locus coeruleus from Alzheimer's disease patients. Based on this, it has been hypothesized that the early loss of noradrenergic projections and the subsequent reduction of noradrenaline brain levels contribute to cognitive dysfunctions and the progression of neurodegeneration. Several studies have focused on analyzing the role of noradrenaline in the development and progression of Alzheimer's disease. In this review we summarize some of the most relevant data describing the alterations of the noradrenergic system normally occurring in Alzheimer's disease as well as experimental studies in which noradrenaline concentration was modified in order to further analyze how these alterations affect the behavior and viability of different nervous cells. The combination of the different studies here presented suggests that the maintenance of adequate noradrenaline levels in the central nervous system constitutes a key factor of the endogenous defense systems that help prevent or delay the development of Alzheimer's disease. For this reason, the use of noradrenaline modulating drugs is proposed as an interesting alternative therapeutic option for Alzheimer's disease.
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页数:25
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