摘要
脑干的蓝斑(LC)神经元发出大量的去甲肾上腺素能(NE)节点到脑部大多数区域,特别是那些涉及认知功能的区域。阿尔茨海默氏病(AD)和唐氏综合征(DS)具有相同的病理,包括显著的蓝斑(LC)变性和去甲肾上腺素能(NE)系统功能障碍。去甲肾上腺素能(NE)节点广泛的损失已与脑内重要的认知、情绪以及执行功能改变相关。同时,去甲肾上腺素能(NE)异常导致认知功能障碍的机制尚不完全清楚,有紧急证据表明,救援NE能系统可以减轻AD和DS患者神经病理学改变和的认知能力下降。增强NE神经递质的治疗策略已经在有限的试验期,到目前为止开展实施的是NE再摄取抑制剂,突触前αβ-肾上腺素能受体拮抗剂,肾上腺素的前体药物,和β-肾上腺素能受体激动剂。在这里,我们研究了AD 和DS中去甲肾上腺素能(NE)系统的改变,并建议NE能系统的救援是针对这两种疾病的认知能力下降的一个合理的治疗策略。
关键词: Adrenergic system
Current Alzheimer Research
Title:Noradrenergic System in Down Syndrome and Alzheimer’s Disease A Target for Therapy
Volume: 13 Issue: 1
Author(s): Cristy Phillips, Atoossa Fahimi, Devsmita Das, Fatemeh S. Mojabi, Ravikumar Ponnusamy and Ahmad Salehi
Affiliation:
关键词: Adrenergic system
摘要: Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer’s disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.
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Cite this article as:
Cristy Phillips, Atoossa Fahimi, Devsmita Das, Fatemeh S. Mojabi, Ravikumar Ponnusamy and Ahmad Salehi , Noradrenergic System in Down Syndrome and Alzheimer’s Disease A Target for Therapy, Current Alzheimer Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567205012666150921095924
DOI https://dx.doi.org/10.2174/1567205012666150921095924 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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