Abstract:This study addresses the effects of induced hyperthermia on post-ischemic rat brain evaluated histologically and/or immunohistochemically after 7-day, 2-month or 6-month survival. Hyperthermia (38.5 degrees - 40 degrees C) maintained (by heating the cage environment to 34-35 degrees C) for two consecutive periods of 5 and 9 h timed, respectively, from 4- and 21-h recirculation following 10-min global ischemia (two-vessel occlusion + hypotension) induced chronic neuronal death that became apparent in the rat fo… Show more
“…Evidence that supports the above-mentioned material from experimental, global, and focal brain ischemia which are followed by recirculation demonstrated strong, abnormal brain staining to the N-terminal of amyloid precursor protein and to the β-amyloid peptide and to the C-terminal of amyloid precursor protein, too. There was noted not only intracellular staining [14, 22, 65–80] but also extracellular one [14, 71, 74, 77, 80, 81]. Fig.…”
Section: Link Between β- and γ-Secretasesmentioning
confidence: 99%
“…A receptor for advanced glycation end products binding β-amyloid peptide on neuronal cells can kill them directly by formatting inflammatory factors or indirectly by activating microglia cells [93, 97]. In contrast, ischemia also induces the production of intracellular β-amyloid peptide what was shown by immunocytochemical investigation [14, 22, 74, 77, 80]. Oligomeric β-amyloid peptide is toxic [12] and initiates a series of events in ischemic brain including the hyperphosphorylation of tau protein that results in severe neurons [11, 20], microglia [99], and oligodendrocytes [100] pathology.…”
Section: Ischemic Cell Deathmentioning
confidence: 99%
“…Thirdly, this review shows that the activation of the positive feedback loop by β- and γ-secretases needs the stress-activated protein kinases signaling cascade which is generated in Alzheimer’s disease apoptosis. In animals, ischemia increases β-amyloid peptide formation [14, 22, 74, 77, 80], accumulation of hyperphosphorylated tau protein, and filament generation similar to the one present in human Alzheimer’s disease brain [17, 18, 20, 106, 107]. This implies that ischemic episodes may develop neuropathological alterations similar to those seen in Alzheimer’s disease patients [24, 103].…”
Section: Ischemia and Pathogenesis Of Sporadic Alzheimer’s Diseasementioning
confidence: 99%
“…The modified proteins and/or their products like β-amyloid peptide that is a product of parent amyloid precursor protein proteolysis can aggregate. When this process starts, proteins form pathological aggregates like amyloid plaques and neurofibrillary tangles [10, 11, 15, 16, 19–22]. Moreover, pathological aggregates can be observed in intra- and extracellular space.…”
Amyloid precursor protein cleavage through β- and γ-secretases produces β-amyloid peptide, which is believed to be responsible for death of neurons and dementia in Alzheimer’s disease. Levels of β- and γ-secretase are increased in sensitive areas of the Alzheimer’s disease brain, but the mechanism of this process is unknown. In this review, we prove that brain ischemia generates expression and activity of both β- and γ-secretases. These secretases are induced in association with oxidative stress following brain ischemia. Data suggest that ischemia promotes overproduction and aggregation of β-amyloid peptide in brain, which is toxic for ischemic neuronal cells. In our review, we demonstrated the role of brain ischemia as a molecular link between the β- and the γ-secretase activities and provided a molecular explanation of the possible neuropathogenesis of sporadic Alzheimer’s disease.
“…Evidence that supports the above-mentioned material from experimental, global, and focal brain ischemia which are followed by recirculation demonstrated strong, abnormal brain staining to the N-terminal of amyloid precursor protein and to the β-amyloid peptide and to the C-terminal of amyloid precursor protein, too. There was noted not only intracellular staining [14, 22, 65–80] but also extracellular one [14, 71, 74, 77, 80, 81]. Fig.…”
Section: Link Between β- and γ-Secretasesmentioning
confidence: 99%
“…A receptor for advanced glycation end products binding β-amyloid peptide on neuronal cells can kill them directly by formatting inflammatory factors or indirectly by activating microglia cells [93, 97]. In contrast, ischemia also induces the production of intracellular β-amyloid peptide what was shown by immunocytochemical investigation [14, 22, 74, 77, 80]. Oligomeric β-amyloid peptide is toxic [12] and initiates a series of events in ischemic brain including the hyperphosphorylation of tau protein that results in severe neurons [11, 20], microglia [99], and oligodendrocytes [100] pathology.…”
Section: Ischemic Cell Deathmentioning
confidence: 99%
“…Thirdly, this review shows that the activation of the positive feedback loop by β- and γ-secretases needs the stress-activated protein kinases signaling cascade which is generated in Alzheimer’s disease apoptosis. In animals, ischemia increases β-amyloid peptide formation [14, 22, 74, 77, 80], accumulation of hyperphosphorylated tau protein, and filament generation similar to the one present in human Alzheimer’s disease brain [17, 18, 20, 106, 107]. This implies that ischemic episodes may develop neuropathological alterations similar to those seen in Alzheimer’s disease patients [24, 103].…”
Section: Ischemia and Pathogenesis Of Sporadic Alzheimer’s Diseasementioning
confidence: 99%
“…The modified proteins and/or their products like β-amyloid peptide that is a product of parent amyloid precursor protein proteolysis can aggregate. When this process starts, proteins form pathological aggregates like amyloid plaques and neurofibrillary tangles [10, 11, 15, 16, 19–22]. Moreover, pathological aggregates can be observed in intra- and extracellular space.…”
Amyloid precursor protein cleavage through β- and γ-secretases produces β-amyloid peptide, which is believed to be responsible for death of neurons and dementia in Alzheimer’s disease. Levels of β- and γ-secretase are increased in sensitive areas of the Alzheimer’s disease brain, but the mechanism of this process is unknown. In this review, we prove that brain ischemia generates expression and activity of both β- and γ-secretases. These secretases are induced in association with oxidative stress following brain ischemia. Data suggest that ischemia promotes overproduction and aggregation of β-amyloid peptide in brain, which is toxic for ischemic neuronal cells. In our review, we demonstrated the role of brain ischemia as a molecular link between the β- and the γ-secretase activities and provided a molecular explanation of the possible neuropathogenesis of sporadic Alzheimer’s disease.
“…High temperature induces structural changes in A β (tangle and plaques) or changes in brain similar to those observed in AD [33]. The conformation of A β 40 at 0–20°C was α -helical, whereas conformational changes of A β 40 towards β -sheet conformation were observed at between 35–45, 60–65, and 80–85°C [13].…”
We present here environmental factors including pH shifts, temperature, and metal ions surrounding Aβ40 monomer to precede the oligomers. We also suggest a new idea to detect Aβ40 oligomers with anti-Aβ40 monoclonal antibody using enzyme-linked immunosorbent assay. This method involves the different sensitivity of the thermal shifts between Aβ40 monomer and the oligomers. The idea is useful for the diagnostics of Alzheimer's disease to detect Aβ40 oligomers in the serum from the patients.
There is increasing evidence for influence of Alzheimer's proteins and neuropathology on ischemic brain injury. This review investigates the relationships between b-amyloid peptide, apolipoproteins, presenilins, tau protein, a-synuclein, inflammation factors, and neuronal survival/ death decisions in brain following ischemic episode. The interactions of these molecules and influence on b-amyloid peptide synthesis and contribution to ischemic brain degeneration and finally to dementia are reviewed. Generation and deposition of b-amyloid peptide and tau protein pathology are important key players involved in mechanisms in ischemic neurodegeneration as well as in Alzheimer's disease. Current evidence suggests that inflammatory process represents next component, which significantly contribute to degeneration progression. Although inflammation was initially thought to arise secondary to ischemic neurodegeneration, recent studies present that inflammatory mediators may stimulate amyloid precursor protein metabolism by upregulation of b-secretase and therefore are able to establish a vicious cycle. Functional brain recovery after ischemic lesion was delayed and incomplete by an injuryrelated increase in the amount of the neurotoxic C-terminal of amyloid precursor protein and b-amyloid peptide. Moreover, ischemic neurodegeneration is strongly accelerated with aging, too. New therapeutic alternatives targeting these proteins and repairing related neuronal changes are under development for the treatment of ischemic brain consequences including memory loss prevention.
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