Association of Selenoprotein P with Alzheimer's Pathology in Human Cortex

Bellinger, Frederick P.; He, Qingping; Bellinger, Miyoko T.; Lin, Yanling; Raman, Arjun V.; White, Lon R.; Berry, Marla J.

doi:10.3233/jad-2008-15313

Cited by 111 publications

(94 citation statements)

References 34 publications

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“…184 SelP presents a characteristic expression pattern within the centre of neuritic (dense-core) plaques. 185 Although a specific action of SelP in AD is still uncertain, its distribution in the brain suggests a role in mitigating the oxidation accompanying plaques. The age-related alteration of other Se-proteins activity in brain of AD patients results in increased oxidative stress and reduced protection against neurodegeneration through redox regulation.…”

Section: Neurological Disordersmentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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Section: Neurological Disordersmentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

View full text Add to dashboard Cite

show abstract

“…SelP gene expression in human brain increases with age [151], and its expression level is higher in AD patients [152]. Moreover, SelP is preferentially associated with amyloid plaques and NFTs [52], which may limit its utilization for synthesis of other selenoproteins.…”

Section: A Mechanistic Model Of Mercury Toxicitymentioning

confidence: 99%

“…Differential competition for uptake between ApoE isoforms and SelP might therefore affect selenoprotein status and vulnerability to oxidative stress. Notably, SelP is physically associated with both Aβ plaques and NFTs in the AD brain [52], further suggesting a role for impaired selenoprotein function in AD pathology.…”

Section: Introductionmentioning

confidence: 99%

Does Inorganic Mercury Play a Role in Alzheimer's Disease? A Systematic Review and an Integrated Molecular Mechanism

Mutter¹,

Curth

Naumann³

et al. 2010

JAD

147

113

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Abstract. Mercury is one of the most toxic substances known to humans. It has been introduced into the human environment and has also been widely used in medicine. Since circumstantial evidence exists that the pathology of Alzheimer's disease (AD) might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review using a comprehensive search strategy. Studies were screened according to a pre-defined protocol. Two reviewers extracted relevant data independent of each other. One thousand and forty one references were scrutinized, and 106 studies fulfilled the inclusion criteria. Most studies were case control or comparative cohort studies. Thirty-two studies, out of 40 testing memory in individuals exposed to inorganic mercury, found significant memory deficits. Some autopsy studies found increased mercury levels in brain tissues of AD patients. Measurements of mercury levels in blood, urine, hair, nails, and cerebrospinal fluid were inconsistent. In vitro models showed that inorganic mercury reproduces all pathological changes seen in AD, and in animal models inorganic mercury produced changes that are similar to those seen in AD. Its high affinity for selenium and selenoproteins suggests that inorganic mercury may promote neurodegenerative disorders via disruption of redox regulation. Inorganic mercury may play a role as a co-factor in the development of AD. It may also increase the pathological influence of other metals. Our mechanistic model describes potential causal pathways. As the single most effective public health primary preventive measure, industrial, and medical usage of mercury should be eliminated as soon as possible.

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“…Cellular Se concentrations are therefore tightly regulated. The regulation of SeP synthesis is central to understanding Se homeostasis and disorders following the failure of homeostasis [5,17,18]. Cellular Se concentration is a key regulator of Se incorporation into SePs and acts mainly at the post-transcriptional level in response to alterations in Se availability [19].…”

Section: Biochemistry Of Selenium and Selenoproteinsmentioning

confidence: 99%

“…Some thirty SePs, mostly enzymes, have been identified, including a series of glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases [1][2][3][4]. The majority play important roles in redox regulation, detoxification, immunity and viral suppression [5][6][7]. Deficiency or low Se status leads to marked changes in many biochemical pathways and a range of pathologies associated with defects of SeP function may occur [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Selenium Biochemistry and Bioavailability: Implications for Animal Agriculture

2015

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Selenium (Se) is an essential trace mineral required for growth, development, immune function, and metabolism. Selenium exerts its biological effects as an integral component of selenoproteins (SePs). Deficiency or low Se status leads to marked changes in many biochemical pathways and a range of pathologies and disorders which are associated with SeP function. Animals, and presumably humans, are able to efficiently utilize nutritionally adequate levels of Se in both organic and inorganic forms. It is now clear that the bioavailability of Se varies depending on the source and chemical form of the Se supplement. There are a range of products available for dietary Se supplementation, however, organic sources have been shown to be assimilated more efficiently than inorganic compounds and are considered to be less toxic and more appropriate as a feed supplement. Yeast enriched with Selenohomoalanthionine (SeHLan) has recently become commercially available, and initial research suggests that it may be an efficacious source for the production of Se enriched animal products.

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Association of Selenoprotein P with Alzheimer's Pathology in Human Cortex

Cited by 111 publications

References 34 publications

Selenium biochemistry and its role for human health

Selenium biochemistry and its role for human health

Does Inorganic Mercury Play a Role in Alzheimer's Disease? A Systematic Review and an Integrated Molecular Mechanism

Selenium Biochemistry and Bioavailability: Implications for Animal Agriculture

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