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Disease Brain (disease + brain)

Distribution by Scientific Domains
Life Sciences57%
Medical Sciences42%

Kinds of Disease Brain

  • alzheimer's disease brain
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    Selected Abstracts

    Amyloid ,-Peptide(1-42) Contributes to the Oxidative Stress and Neurodegeneration Found in Alzheimer Disease Brain

    BRAIN PATHOLOGY, Issue 4 2004
    D. Allan Butterfield
    Oxidative stress is extensive in Alzheimer disease (AD) brain. Amyloid ,-peptide (1,42) has been shown to induce oxidative stress and neurotoxicity in vitro and in vivo. Genetic mutations that result in increased production of A,1,42 from amyloid precursor protein are associated with an early onset and accelerated pathology of AD. Consequently, A,1,42 has been proposed to play a central role in the pathogenesis of AD as a mediator of oxidative stress. In this review, we discuss the role of A,1,42 in the lipid peroxidation and protein oxidation evident in AD brain and the implications of such oxidative stress for the function of various proteins that we have identified as specifically oxidized in AD brain compared to control, using proteomics methods. Additionally, we discuss the critical role of methionine 35 in the oxidative stress and neurotoxic properties exhibited by A,1,42. [source]

    Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity

    GLIA, Issue 10 2008
    Kryslaine O. Lopes
    Abstract Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34,97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 ± 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. © 2008 Wiley-Liss, Inc. [source]

    Astrocyte modulation of in vitro ,-amyloid neurotoxicity

    GLIA, Issue 3 2004
    Silvia Paradisi
    Abstract In Alzheimer's disease brain, ,-amyloid (A,) deposition is accompanied by astrocyte activation, whose role in the pathogenesis of the disease is still unclear. To explore the subject, we compared A, neurotoxicity in pure hippocampal cultures and neuronal-astrocytic cocultures, where astrocytes conditioned neurons but were not in contact with them or A,. In the presence of astrocytes, neurons were protected from A, neurotoxicity. Neuritic dystrophy was reduced, synapses were partially preserved, and apoptosis was contrasted. The protection disappeared when astrocytes were also treated with A,, suggesting that A,-astrocyte interaction is deleterious for neurons. This was supported by comparing A, neurotoxicity in pure neurons and neurons grown on astrocytes. In this case, where astrocytes were also in contact with A,, neuritic damage was enhanced and expression of synaptic vesicle proteins decreased. Our results suggest that astrocytes can protect neurons from A, neurotoxicity, but when they interact with A,, the protection is undermined and neurotoxicity enhanced. © 2004 Wiley-Liss, Inc. [source]

    Inhibition of A, aggregation and neurotoxicity by the 39-kDa receptor-associated protein

    JOURNAL OF NEUROCHEMISTRY, Issue 5 2010
    Megan L. Kerr
    J. Neurochem. (2010) 112, 1199,1209. Abstract Aggregation of ,-amyloid protein (A,) to form oligomers is considered to be a key step in generating neurotoxicity in the Alzheimer's disease brain. Agents that bind to A, and inhibit oligomerization have been proposed as Alzheimer's disease therapeutics. In this study, we investigated the binding of fluorescein-labeled A,1,42 (FluoA,1,42) to SH-SY5Y neuroblastoma cells and examined the effect of the 39-kDa receptor-associated protein (RAP), on the A, cell interaction. FluoA,1,42 bound to the cells in a punctate pattern. Surprisingly, when RAP was added to the incubations, FluoA,1,42 and RAP were found to be co-localized on the cell surface, suggesting that RAP and A, may bind to each other. Experiments using the purified proteins confirmed that a RAP,A, complex was stable and resistant to sodium dodecyl sulfate. RAP also inhibited A, oligomerization. We next examined whether RAP could inhibit the neurotoxic effects of A,. Addition of A,1,42 to SH-SY5Y cells caused an increase in intracellular Ca2+ that was inhibited by treatment of the A, peptide with RAP. RAP also blocked an A,-induced inhibition of long-term memory consolidation in 1-day-old chicks. This study demonstrates that RAP binds to A, and is an inhibitor of the neurotoxic effects of A,. [source]

    The p53 homologue p73 accumulates in the nucleus and localizes to neurites and neurofibrillary tangles in Alzheimer disease brain

    NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2004
    C. Wilson
    The molecular mechanisms that regulate neuronal survival vs. death during Alzheimer disease (AD) remain unclear. Nonetheless, a number of recent studies indicate that increased expression or altered subcellular distribution of numerous cell cycle proteins during AD may contribute to disease pathogenesis. Because homologues of p53, a key regulatory protein in the cell cycle, such as p73, have been identified and shown to participate in cellular differentiation and death pathways, we examined the expression and distribution of p73 in the hippocampus of eight control and 16 AD subjects. In control subjects, hippocampal pyramidal neurones exhibit p73 immunoreactivity that is distributed predominately in the cytoplasm. In AD hippocampus, increased levels of p73 are located in the nucleus of pyramidal neurones and p73 is located in dystrophic neurites and cytoskeletal pathology. Immunoblot analysis confirmed the presence of p73 in the hippocampus. These data indicate that p73 is expressed within hippocampal pyramidal neurones and exhibits altered subcellular distribution in AD. [source]

    Modulation of histamine H3 receptors in the brain of 6-hydroxydopamine-lesioned rats

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000
    Oleg V. Anichtchik
    Abstract Parkinson's disease is a major neurological disorder that primarily affects the nigral dopaminergic cells. Nigral histamine innervation is altered in human postmortem Parkinson's disease brains. However, it is not known if the altered innervation is a consequence of dopamine deficiency. The aim of the present study was to investigate possible changes in the H3 receptor system in a well-characterized model of Parkinson's disease , the 6-hydroxydopamine (6-OHDA) lesioned rats. Histamine immunohistochemistry showed a minor increase of the fibre density index but we did not find any robust increase of histaminergic innervation in the ipsilateral substantia nigra on the lesioned side. In situ hybridization showed equal histidine decarboxylase mRNA expression on both sides in the posterior hypothalamus. H3 receptors were labelled with N-alpha-[3H]-methyl histamine dihydrochloride ([3H] NAMH). Upregulation of binding to H3 receptors was found in the substantia nigra and ventral aspects of striatum on the ipsilateral side. An increase of GTP-,-[35S] binding after H3 agonist activation was found in the striatum and substantia nigra on the lesioned side. In situ hybridization of H3 receptor mRNA demonstrated region-specific mRNA expression and an increase of H3 receptor mRNA in ipsilateral striatum. Thus, the histaminergic system is involved in the pathological process after 6-OHDA lesion of the rat brain at least through H3 receptor. On the later stages of the neurotoxic damage, less H3 receptors became functionally active. Increased H3 receptor mRNA expression and binding may, for example, modulate GABAergic neuronal activity in dopamine-depleted striatum. [source]

    Specific association of small heat shock proteins with the pathological hallmarks of Alzheimer's disease brains

    NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2006
    M. M. M. Wilhelmus
    The small heat shock protein family (sHsp) comprises molecular chaperones able to interact with incorrectly folded proteins. Alzheimer's disease (AD) is characterized by pathological lesions such as senile plaques (SPs), cerebral amyloid angiopathy (CAA) and neurofibrillary tangles (NFTs), predominantly consisting of the incorrectly folded proteins amyloid-, (A,) and tau respectively. The aim of this study was to investigate the association of the chaperones Hsp20, HspB2, ,B-crystallin and Hsp27 with the pathological lesions of AD brains. For this purpose, a panel of well-characterized antibodies directed against these sHsps was used in immunohistochemistry and immunoblotting. We observed extracellular expression of Hsp20, Hsp27 and HspB2 in classic SPs, and Hsp20 expression in diffuse SPs. In addition, extracellular expression of HspB2 was observed in CAA. Both Hsp27 and ,B-crystallin were also observed in astrocytes associated with both SPs and CAA. Furthermore, none of the sHsps were observed in NFTs in AD brains. We conclude that specific sHsp species may be involved in the pathogenesis of either SPs or CAA in AD. [source]