中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (7): 1158-1176.doi: 10.4103/1673-5374.251192

• 综述:退行性病与再生 • 上一篇    下一篇

在阿尔茨海默病动物模型中通过免疫调节剂改善阿尔茨海默病的病理学和认知缺陷

  

  • 出版日期:2019-07-15 发布日期:2019-07-15

Amelioration of Alzheimer’s disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer’s disease

Bridget Martinez 1, 2, 3 , Philip V. Peplow 4   

  1. 1 Department of Molecular & Cellular Biology, University of California, Merced, Merced, CA, USA
    2 Department of Medicine, St. Georges University School of Medicine, Grenada
    3 Department of Physics and Engineering, Los Alamos National Laboratory, Los Alamos, NM, USA
    4 Department of Anatomy, University of Otago, Dunedin, New Zealand
  • Online:2019-07-15 Published:2019-07-15
  • Contact: Philip V. Peplow, PhD, phil.peplow@otago.ac.nz

摘要:

orcid: 0000-0001-5468-1989 (Philip V. Peplow)

Abstract:

The most common age-related neurodegenerative disease is Alzheimer’s disease (AD) characterized by aggregated amyloid-β (Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles, together with loss of cholinergic neurons, synaptic alterations, and chronic inflammation within the brain. These lead to progressive impairment of cognitive function. There is evidence of innate immune activation in AD with microgliosis. Classically-activated microglia (M1 state) secrete inflammatory and neurotoxic mediators, and peripheral immune cells are recruited to inflammation sites in the brain. The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects. Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials. Treatment with immunomodulatory/anti-inflammatory agents early in the disease process, while not preventive, is able to inhibit the inflammatory consequences of both Aβ and tau aggregation. The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD. The majority of the animal studies reviewed had used transgenic models of early-onset AD. More effort needs to be given to creat models of late-onset AD. The effects of a combinational therapy involving two or more of the tested pharmaceutical agents, or one of these agents given in conjunction with one of the cell-based therapies, in an aged animal model of AD would warrant investigation.

Key words: Alzheimer’s disease, neuropathology, cognitive deficits, behavioral deficits, immunomodulatory agents, animal models, amyloid deposits, gliosis