Metallothionein biology in the ageing and neurodegenerative brain

Dittmann, J.; Fung, Samantha J.; Vickers, James C.; Chuah, Mi; Chung, Roger S.; West, Adrian K.

doi:10.1007/bf03033779

Cited by 22 publications

(22 citation statements)

References 55 publications

(49 reference statements)

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“…In concordance with such a pathogenic relationship, it has been found that AD concentrations of metal ions, such as iron, zinc and copper, are markedly elevated particularly in those areas most severely affected by the disease [42,111]. At the same time, it appeared that levels of metal binding proteins remained virtually unaltered or were even decreased in AD [114][115][116]. Hence, the picture emerges that redox interactions between Aβ, APP, and trace metal ions, on one hand, and activated microglial cells, on the other, form the centre of a feed forward loop wherein Aβ amyloidosis and oxidative stress appear to be potent reinforcing phenomena [92].…”

Section: Oxidative Stress In Alzheimer's Diseasementioning

confidence: 86%

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

Muiswinkel¹,

2005

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A large body of evidence indicates that oxidative stress is a salient pathological feature in many neurodegenerative diseases, including Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In addition to signs of systemic oxidative stress, at the biochemical and neuropathological level, neuronal degeneration in these disorders has been shown to coincide with several markers of oxidative damage to lipids, nucleic acids, and proteins in affected brain regions. Neuroinflammatory processes, often associated with the induction of free radical generating enzymes and the accumulation of reactive astrocytes and microglial cells, are considered as a major source of oxidative stress. Given the pathogenic impact of oxidative stress and neuroinflammation, therapeutic strategies aimed to blunt these processes are considered an effective way to confer neuroprotection. Recently, the nuclear transcription factor Nrf2, that binds to the antioxidant response element (ARE) in gene promoters, has been reported to constitute a key regulatory factor in the co-ordinate induction of a battery of endogenous cytoprotective genes, including those encoding for both antioxidant- and anti-inflammatory proteins. In the present review, besides discussing recent evidence underscoring the thesis that the Nrf2-ARE signalling pathway is an attractive therapeutic target for neurodegenerative diseases, we advocate the view that chemopreventive agents might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.

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Section: Oxidative Stress In Alzheimer's Diseasementioning

confidence: 86%

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

Muiswinkel¹,

2005

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“…Among these, the metallothioneins Mt1a/Mt2 and Sult1a1 have important roles in the immune and inflammatory response as scavengers of free radicals or detoxification enzymes, respectively. Interestingly, Mt2, which exhibits increased expression in astrocytes upon brain injury (13,17), was induced by Ͼ12-fold, representing one of the most strongly activated genes at this postinfection time point (Table 6). Moreover, expression of critical components of the classical complement system (C1qb, C1s, and C4a) and interferon regulatory factor 7 (Irf7), along with interferon-stimulated GTPase2 (Iigp2), were increased.…”

Section: Vol 80 2006 Brain Transcriptional Response To Prv Infectiomentioning

confidence: 99%

Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain

Paulus

Sollars

Pickard

et al. 2006

J Virol

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Mammalian alphaherpesviruses normally establish latent infections in ganglia of the peripheral nervous system in their natural hosts. Occasionally, however, these viruses spread to the central nervous system (CNS), where they cause damaging, often fatal, infections. Attenuated alphaherpesvirus derivatives have been used extensively as neuronal circuit tracers in a variety of animal models. Their circuit-specific spread provides a unique paradigm to study the local and global CNS response to infection. Thus, we systematically analyzed the host gene expression profile after acute pseudorabies virus (PRV) infection of the CNS using Affymetrix GeneChip technology. Rats were injected intraocularly with one of three selected virulent and attenuated PRV strains. Relative levels of cellular transcripts were quantified from hypothalamic and cerebellar tissues at various times postinfection. The number of cellular genes responding to infection correlated with the extent of virus dissemination and relative virulence of the PRV strains. A total of 245 out of 8,799 probe sets, corresponding to 182 unique cellular genes, displayed increased expression ranging from 2-to more than 100-fold higher than in uninfected tissue. Over 60% thereof were categorized as immune, proinflammatory, and other cellular defense genes. Additionally, a large fraction of infection-induced transcripts represented cellular stress responses, including glucocorticoid-and redox-related pathways. This is the first comprehensive in vivo analysis of the global transcriptional response of the mammalian CNS to acute alphaherpesvirus infection. The differentially regulated genes reported here are likely to include potential diagnostic and therapeutic targets for viral encephalitides and other neurodegenerative or neuroinflammatory diseases.

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“…Among the micronutrients, Zinc (Zn) is essential in the elderly regarding its impact on immune functions (Bogden, 2004), age-related changes on bone mass (Lowe et al, 2002), cognitive functions (Mocchegiani et al, 2005) and oxidative stress (Mocchegiani et al, 2004;Dittmann et al, 2005). Its role in healthy ageing is also particularly important as it prevents neoplastic cell growth and is involved in DNA and RNA repair (Tudor et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Zinc intake and status in middle-aged and older European subjects: the ZENITH study

et al. 2005

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Objective: Inadequate intakes of micronutrients in elderly negatively affect the nutritional status. Zinc is an essential micronutrient in the elderly, especially in relation to its impact on immune function, bone mass, cognitive function and oxidative stress. However, data are lacking on zinc intake and status during normal ageing. In this study, we evaluate the intake and status of zinc in late middle-aged and older free-living subjects. Design: Dietary zinc intake and zinc status in 188 middle-aged subjects from Clermont-Ferrand (Fr) and Coleraine (UK), and in 199 older subjects from Grenoble (Fr) and Roma (It) were assessed at the entry in the ZENITH study. Results: In relation to the zinc RDA for people older than 55 y, zinc intakes in most of the middle-aged and older subjects (more than 96%) in the present study were adequate. Older people had significantly lower (Po0.01) energy intakes as compared to middle-aged. Zinc intake expressed per MJ was also significantly (Po0.01) higher in older people compared to middle-aged. Erythrocyte and urinary zinc concentrations were significantly (Po0.001) higher in middle-aged subjects compared to older ones. The prevalence of biological Zn deficiency in free-living ageing European people was low (o5%). Conclusion:The results of the present study showed a relatively low prevalence of zinc deficiencies in healthy free-living late middle-age and older subjects. These results should be useful for health professionals to have reference data on zinc intake and status for a healthy ageing.

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Metallothionein biology in the ageing and neurodegenerative brain

Cited by 22 publications

References 55 publications

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain

Zinc intake and status in middle-aged and older European subjects: the ZENITH study

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