1.Influence of apolipoprotein E and its receptors on cerebral amyloid precursor protein metabolism following traumatic brain injury.
Chinese Journal of Traumatology 2012;15(3):183-187
Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals in our society, and globally the incidence of TBI is rising sharply. Mounting evidence has indicated that apolipoprotein E (apoE: protein; APOE: gene) genotype influences the outcome after TBI. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of lipid distribution, dysfunction of mitochondrial energy production, oxidative stress and increases intracellular calcium in response to injury. This paper reviews the current state of knowledge regarding the influence of apoE and its receptors on cerebral amyloid beta-protein precursor metabolism following TBI.
Amyloid beta-Peptides
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Apolipoproteins E
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Brain Injuries
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metabolism
;
Humans
2.Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer's Disease and Attenuate AD-type Pathology in a Mouse Model.
Jie-Ming JIAN ; Dong-Yu FAN ; Ding-Yuan TIAN ; Yuan CHENG ; Pu-Yang SUN ; Cheng-Rong TAN ; Gui-Hua ZENG ; Chen-Yang HE ; Ye-Ran WANG ; Jie ZHU ; Xiu-Qing YAO ; Yan-Jiang WANG ; Yu-Hui LIU
Neuroscience Bulletin 2022;38(9):1025-1040
Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology*
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Amyloid beta-Peptides/metabolism*
;
Amyloid beta-Protein Precursor/metabolism*
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Animals
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Disease Models, Animal
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Humans
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Mice
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Mice, Transgenic
3.Alzheimer's disease: advance in researches on Beta-amyloid protein.
Jianhui LIU ; Yongming BAO ; Lijia AN
Journal of Biomedical Engineering 2003;20(2):371-374
The pathogenesis and treatment of Alzheimer's disease (AD) have developed into the frontier with the aging of people in the world. Meanwhile, they are the most difficult steps in the research on this degenerative disease of the nervous system. The over-deposition of beta-amyloid protein in nervous system is the most important feature. The formation and influencing factors of beta-amyloid protein are summarized in this paper. Furthermore, the methods and advance in treatment of AD are reviewed especially.
Aged
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Alzheimer Disease
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drug therapy
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metabolism
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Amyloid beta-Peptides
;
metabolism
;
Brain
;
metabolism
;
Humans
;
Middle Aged
4.Research advances in the role of Rab GTPases in Alzheimer's disease.
Jing ZHANG ; Hai-Tian JIANG ; Dao-Bin HAN ; Hui YU ; Lu-Wen WANG ; Bo SU
Acta Physiologica Sinica 2023;75(6):817-835
Extracellular deposition of β-amyloid (Aβ) and intracellular hyperphosphorylated tau are the predominant pathological changes in Alzheimer's disease (AD). Increasing evidence demonstrates a critical role of a variety of small GTPases, namely Ras-related proteins (Rabs), in the pathogenesis of AD. As crucial regulators of intracellular membrane trafficking, alteration in Rab protein expression and function represents one of the primary factors contributing to the abnormal membrane trafficking in AD. Additionally, the Rab GTPases are also involved in the development of Aβ, tau and other pathological changes associated with AD. In this article, we conduct a comprehensive review on the primary functions of multiple Rab proteins and their involvement in the pathogenesis of AD.
Humans
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Alzheimer Disease
;
rab GTP-Binding Proteins/metabolism*
;
Amyloid beta-Peptides/metabolism*
;
tau Proteins/metabolism*
5.Focal-type, but not Diffuse-type, Amyloid Beta Plaques are Correlated with Alzheimer's Neuropathology, Cognitive Dysfunction, and Neuroinflammation in the Human Hippocampus.
Fan LIU ; Jianru SUN ; Xue WANG ; Sixuan JIN ; Fengrun SUN ; Tao WANG ; Bo YUAN ; Wenying QIU ; Chao MA
Neuroscience Bulletin 2022;38(10):1125-1138
Amyloid beta (Aβ) plaques are one of the hallmarks of Alzheimer's disease (AD). However, currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans. It has been found that there are different types of Aβ plaque (diffuse and focal types) in the postmortem human brain. In this study, we aimed to investigate the correlations among different types of Aβ plaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China. The results indicated that focal plaques, but not diffuse plaques, significantly increased with age in the human hippocampus. We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes (measured by the "ABC" scoring system) and cognitive decline (measured by the Everyday Cognitive Insider Questionnaire). Furthermore, most of the focal plaques were co-localized with neuritic plaques (identified by Bielschowsky silver staining) and accompanied by microglial and other inflammatory cells. Our findings suggest the potential of using focal-type but not general Aβ plaques as biomarkers for the neuropathological evaluation of AD.
Alzheimer Disease/pathology*
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Amyloid beta-Peptides/metabolism*
;
Amyloid beta-Protein Precursor
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Brain/pathology*
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Cognitive Dysfunction/pathology*
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Hippocampus/metabolism*
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Humans
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Neuroinflammatory Diseases
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Plaque, Amyloid/pathology*
7.Alzheimer's disease and oxidative stress.
Dehong YU ; Chaoliang WEI ; Yongming BAO ; Lijia AN
Journal of Biomedical Engineering 2006;23(5):1142-1148
Alzheimer's disease (AD) has abstracted many scientists' interests with the aging of people in the world, but its mechanisms are still remaining unclear. This review will focus on some of the mediators of oxidative stress occurring in AD pathology and their possible role in the AD pathogenesis. Meanwhile, antioxidant approaches for the prevention and treatment of AD are discussed.
Alzheimer Disease
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enzymology
;
metabolism
;
therapy
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Amyloid beta-Peptides
;
metabolism
;
Humans
;
Oxidative Stress
8.Applications of AFM in mechanism study of Alzheimer's disease.
Jianxiu WANG ; Tiebin YANG ; Desheng WANG
Journal of Biomedical Engineering 2007;24(6):1428-1431
Atomic force microscope (AFM) has become a well-established technique for biological sample imaging under physiological conditions. The unique capacity to produce nanometer scale resolution images with simple specimen preparation enables AFM to serve as a powerful tool in neurobiology research. Extensive studies suggest that the conversion of beta-amyloid (Abeta) peptide from soluble forms into fibrillar structure is a key factor in the pathogenesis of Alzheimer's disease (AD). AFM has provided useful insights at all stages of Abeta fibrillization, thus making therapeutic strategy possible. In this brief review, the principles and techniques of AFM and their effects on the pathogenetic study of AD, especially on the study of Abeta and Abeta oligomer are outlined.
Alzheimer Disease
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metabolism
;
pathology
;
Amyloid beta-Peptides
;
metabolism
;
Humans
;
Microscopy, Atomic Force
10.Effect of Regulatory Network of Exosomes and microRNAs on Neurodegenerative Diseases.
Dong LI ; You-Ping LI ; Yun-Xiang LI ; Xiao-Hua ZHU ; Xiao-Gang DU ; Min ZHOU ; Wen-Bin LI ; Hong-Yan DENG
Chinese Medical Journal 2018;131(18):2216-2225
ObjectiveA comprehensive review of the network regulation of exosomes and microRNAs (miRNAs) in neurodegenerative diseases was done, centering on the mechanism of the formation of exosomes and miRNAs and the sorting mechanism of exosomal miRNAs, with the aim to provide a theoretical basis in the search of biomarkers and the treatment of neurodegenerative diseases.
Data SourcesThe comprehensive search used online literature databases including NCBI PubMed, Web of Science, Google Scholar, and Baidu Scholar.
Study SelectionThe study selection was based on the following keywords: exosomes, miRNAs, central nervous system (CNS), and neurodegenerative diseases. The time limit for literature retrieval was from the year 2000 to 2018, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.
ResultsExosomes are the smallest nanoscale membranous microvesicles secreted by cells and contain important miRNAs, among other rich contents. In the CNS, exosomes can transport amyloid β-protein, α-synuclein, Huntington-associated protein 1, and superoxide dismutase I to other cells. These events relieve the abnormal accumulation of proteins and aggravating neurological diseases. In some neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, miRNAs are pathologically altered as an inexorable course, suggesting that miRNAs may contribute neurodegeneration. Exosomes and miRNAs form a network to regulate the homeostasis of the CNS, both synergistically and individually.
ConclusionThe network of exosomes and miRNAs that regulates CNS homeostasis is a promising biomarker for the diagnosis and treatment of neurodegenerative diseases.
Alzheimer Disease ; Amyloid beta-Peptides ; Exosomes ; Humans ; MicroRNAs ; Neurodegenerative Diseases ; genetics ; metabolism