Mutated tau, amyloid and neuroinflammation in Alzheimer disease—A brief review

Hung, Aaron See-Long; Liang, Yong; Chow, Tony C. H.; Tang, Hong; Wu, Sharon L.; Wai, Maria Sen Mun; Yew, David T.

doi:10.1016/j.proghi.2016.01.001

Cited by 39 publications

(23 citation statements)

References 51 publications

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“…). As many as 50 ‘amyloid’ diseases are now established (Ankarcrona et al ., ; Buell, Dobson & Knowles, ; Dobson, ; Hung et al ., ; Ke et al ., ; Kholová & Niessen, ; Knowles, Vendruscolo & Dobson, ; Siakallis, Tziakouri‐Shiakalli & Georgiades, ), in which normally soluble proteins fold to form unusual, insoluble amyloid fibril forms and may become on‐ and off‐pathway oligomers that are particularly important for cytotoxicity (Ke et al ., ). Their general structural hallmark is a much greater content of β‐sheets than the soluble protein, arranged perpendicular to the fibre axis (Dobson, ; Eisenberg & Jucker, ; Langkilde et al ., ; Maji et al ., ; Makin et al ., ; Morris & Serpell, ; Serpell, ; Stromer & Serpell, ; Tsemekhman et al ., ; Tycko & Wickner, ).…”

Section: Step 6: Induction Of Fibrin Amyloid Formation By ‘Iron’ Lpsmentioning

confidence: 98%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.

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Section: Step 6: Induction Of Fibrin Amyloid Formation By ‘Iron’ Lpsmentioning

confidence: 98%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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“…Alzheimer's disease affects around 30 million patients worldwide. The majority of patients are sporadic and of late onset (around and over 65 years old) while only 5% of patients have early onset and related to genetic factors (Blennow et al, 2006 ; Burns and Iliffe, 2009 ; Querfurth and LaFerla, 2010 ; Hung et al, 2016 ). Dementia is the major manifestation of the disease, starting initially with the loss of short term memory (Hung et al, 2016 ).…”

Section: Exosomes In Chronic Neurodegenerative Diseasesmentioning

confidence: 99%

“…The majority of patients are sporadic and of late onset (around and over 65 years old) while only 5% of patients have early onset and related to genetic factors (Blennow et al, 2006 ; Burns and Iliffe, 2009 ; Querfurth and LaFerla, 2010 ; Hung et al, 2016 ). Dementia is the major manifestation of the disease, starting initially with the loss of short term memory (Hung et al, 2016 ). The past 30 years of Alzheimer's disease research have led to the certain proof that accumulation of abnormally folded amyloid β (Aβ) and tau proteins (hyper-phosphorylated tau; p-tau) in amyloid plaques and neuronal tangles, respectively, are causally connected to the typical neurodegenerative process in patients' brains (Karran et al, 2011 ; De Strooper and Karran, 2016 ; Scheltens et al, 2016 ).…”

Section: Exosomes In Chronic Neurodegenerative Diseasesmentioning

confidence: 99%

“…By now, some notions about Alzheimer's disease hold true (Hung et al, 2016 ): (i) neurons are the primary cells dying, by apoptosis, in brains; (ii) plaques conduct to develop death enzymes in neurons, such as caspases, in particular, caspase 6 is an apoptotic cysteine protease which induces disease progression promoting neurodegeneration (Vaidya et al, 2011 ); (iii) brain derived neurotrophic factor (BDNF) has several roles in synaptic plasticity and neuronal survival and it is downregulated in Alzheimer's disease (Janel et al, 2017 ); (iv) in Alzheimer patients, function and levels of adhesion molecules viable for synapses are affected, e.g., synaptic cell adhesion molecules which are glycoproteins of cell surface (Leshchyns'ka and Sytnyk, 2016 ) (v) Alzheimer brains are characterized by a decrease of neurotransmitters, primary acetylcholine, but also catecholamine, glutamate, and serotonin (Selkoe and Schenk, 2003 ; Hung et al, 2016 ).…”

Section: Exosomes In Chronic Neurodegenerative Diseasesmentioning

confidence: 99%

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Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

Ciregia

Urbani

Palmisano

2017

Front. Mol. Neurosci.

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Extracellular vesicles (EVs) can be classified into apoptotic bodies, microvesicles (MVs), and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM), neuroblastoma (NB), medulloblastoma (MB), and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis.

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“…However, the etiology of AD is not well understood. A lot of studies indicate that the major pathological characteristics of AD include abnormal deposition of amyloid beta (Aβ) and tau protein in brain, the loss of synapses and neurons, and the neurofibrillary tangles [ 6 – 9 ]. Besides, other researches find some defects may be also involved in the development of AD, such as vasculopathy, lipidosis, autophagy and lysosomal defects, etc [ 10 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

The association of MPO gene promoter polymorphisms with Alzheimer’s disease risk in Chinese Han population

2017

Oncotarget

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AimThe objective of this study was to explore the genetic association of myeloperoxidase (MPO) gene polymorphisms with risk of Alzheimer's disease (AD).MethodsBlood samples were collected from 116 AD patients and 134 age and gender matched healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to confirm MPO polymorphisms in promoter region. Plasma concentration of MPO was detected by enzyme-linked immuno sorbent assay. Genotype distributions of MPO polymorphisms were compared by χ2 test between the two groups. The status of linkage disequilibrium between MPO two polymorphisms was detected using Haploview. MPO concentrations were analyzed by non-parametric test.ResultsMPO rs2333227 polymorphism was positively associated with AD risk, especially under the AA+GA vs. GG and A vs. G genetic models (P=0.042, OR=1.719, 95%CI=1.017-2.906; P=0.041, OR=1.582, 95%CI=1.016-2.463). While, rs34097845 polymorphism significantly decreased the risk of AD, particularly GA and AA+GA genotypes (P=0.048, OR=0.555, 95%CI=0.308-0.998; P=0.042, OR=0.552, 95%CI=0.310-0.983). In addition, rs2333227 genotypes affected the plasma concentration of MPO. But for rs34097845 polymorphism, only GA genotype exhibited significant association with MPO concentration.ConclusionPolymorphisms in the promoter region of MPO distinctly contribute to AD risk possibly through regulating MPO concentration. Present results should be confirmed by further studies.

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Mutated tau, amyloid and neuroinflammation in Alzheimer disease—A brief review

Cited by 39 publications

References 51 publications

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

The association of MPO gene promoter polymorphisms with Alzheimer’s disease risk in Chinese Han population

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