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Beta-amyloid Peptide (beta-amyloid + peptide)
Selected AbstractsBeta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N -formyl peptide receptorsGLIA, Issue 13 2008Tursonjan Tokay Abstract Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that ,-amyloid peptide (A,) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of A, in cultured rat astrocytes. A,25,35 and the N -formyl peptide receptor (FPR) agonist N -formyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC50 value of ,2 ,M. The stimulatory effects of A,25,35 and the FPR agonists fMLF and N -formyl-Met-Met-Met (fMMM) on endozepine release were abrogated by the FPR antagonist N - t -Boc-Phe-Leu-Phe-Leu-Phe. In contrast, A,25,35 increased DBI mRNA expression through a FPR-independent mechanism. A,25,35 induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of A,25,35 on endozepine release was blocked by the adenylyl cyclase inhibitor somatostatin, the protein kinase A (PKA) inhibitor H89, the phospholipase C inhibitor U73122, the protein kinase C (PKC) inhibitor chelerythrine and the ATP binding cassette transporter blocker glyburide. Taken together, these data demonstrate for the first time that A,25,35 stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC. © 2008 Wiley-Liss, Inc. [source] The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25,35 in middle-aged ratsJOURNAL OF PINEAL RESEARCH, Issue 2 2002Y. X. Shen This work investigated the ability of melatonin to prevent oxidative damage in brain tissue induced by injection of beta-amyloid peptide 25,35 (A,25,35) in middle-aged rats. The Morris water maze was used to evaluate the cognitive function of the rats. Thiobarbituric acid-reactive substances and antioxidative enzymes (superoxide dismutase and glutathione peroxidase) activities were measured. It was found that injection of (A,25,35) (20 ,g) into the rat hippocampus caused an increase in the latency (the time to find the platform), the total swimming distance to the platform, and the starting angles in (A,25,35)-treated rats. Furthermore, a significant rise in lipid peroxidation and decrease in antioxidative enzyme activities in brain tissue were found. Melatonin (0.1, 1, and 10 mg/kg, i.g. × 10 days) improved the spatial resolution of amnesic rats in the Morris water maze test. Meanwhile, melatonin antagonized the lipid peroxidation in both the mitochondria (P < 0.01) at the doses of 0.1, 1.0, and 10 mg/kg and in the cytoplasm at the doses of 0.1 and 1.0 mg/kg. Also in the amnesic rats, melatonin (0.1, 1.0, and 10 mg/kg, i.g. × 10 days) stimulated the antioxidative enzyme activities. The results show that melatonin effectively reduced lipid peroxidation and enhanced the antioxidative enzyme activities in A,25,35 -treated rats, which may contribute to the improvement of rats' learning and memory impaired by A,25,35. [source] Medicinal chemistry approaches for the treatment and prevention of Alzheimer's diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2003S.O. Bachurin Abstract Alzheimer's disease (AD) is the most common form of dementia, which is characterised by progressive deterioration of memory and higher cortical functions that ultimately result in total degradation of intellectual and mental activities. Modern strategies in the search of new therapeutic approaches are based on the morphological and biochemical characteristics of AD, and focused on following directions: agents that compensate the hypofunction of cholinergic system, agents that interfere with the metabolism of beta-amyloid peptide, agents that protect nerve cells from toxic metabolites formed in neurodegenerative processes, agents that activate other neurotransmitter systems that indirectly compensate for the deficit of cholinergic functions, agents that affect the process of the formation of neurofibrillary tangles, anti-inflammatory agents that prevent the negative response of nerve cells to the pathological process. The goal of the present review is the validation and an analysis from the point of view of medicinal chemistry of the principles of the directed search of drugs for the treatment and prevention of AD and related neurodegenerative disorders. It is based on systematization of the data on biochemical and structural similarities in the interaction between physiologically active compounds and their biological targets related to the development of such pathologies. The main emphasis is on cholinomimetic, anti-amyloid and anti-metabolic agents, using the data that were published during the last 3 to 4 years, as well as the results of clinical trials presented on corresponding websites. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 48,88, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10026 [source] Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disordersMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 2 2006Silvia Mandel Abstract Neurodegeneration in Parkinson's, Alzheimer's, or other neurodegenerative diseases appears to be multifactorial, where a complex set of toxic reactions, including oxidative stress (OS), inflammation, reduced expression of trophic factors, and accumulation of protein aggregates, lead to the demise of neurons. One of the prominent pathological features is the abnormal accumulation of iron on top of the dying neurons and in the surrounding microglia. The capacity of free iron to enhance and promote the generation of toxic reactive oxygen radicals has been discussed numerous times. The observations that iron induces aggregation of inert ,-synuclein and beta-amyloid peptides to toxic aggregates have reinforced the critical role of iron in OS-induced pathogenesis of neurodegeneration, supporting the notion that a combination of iron chelation and antioxidant therapy may be one significant approach for neuroprotection. Tea flavonoids (catechins) have been reported to possess divalent metal chelating, antioxidant, and anti-inflammatory activities, to penetrate the brain barrier and to protect neuronal death in a wide array of cellular and animal models of neurological diseases. This review aims to shed light on the multipharmacological neuroprotective activities of green tea catechins with special emphasis on their brain-permeable, nontoxic, transitional metal (iron and copper)-chelatable/radical scavenger properties. [source] Urea-based two-dimensional electrophoresis of beta-amyloid peptides in human plasma: Evidence for novel A, speciesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 20 2007Juan Manuel Maler Abstract The detailed analysis of ,-amyloid (A,) peptides in human plasma is still hampered by the limited sensitivity of available mass spectrometric methods and the lack of appropiate ELISAs to measure A, peptides other than A,1,38, A,1,40, and A,1,42. By combining high-yield A, immuno precipitation (IP), IEF, and urea-based A,-SDS-PAGE-immunoblot, at least 30 A,-immunoreactive spots were detected in human plasma samples as small as 1.6,mL. This approach clearly resolved A, peptides A,1,40, A,1-42, A,1-37, A,1-38, A,1-39, the N-truncated A,2,40, A,2,42, and, for the first time, also A,1,41. Relative quantification indicated that A,1,40 and A,1,42 accounted for less than 60% of the total amount of A, peptides in plasma. All other A, peptides appear to be either C-terminally or N-terminally truncated forms or as yet uncharacterized A, species which migrated as trains of spots with distinct pIs. The A, pattern found in cerebrospinal fluid (CSF) was substantially less complex. This sensitive method (2-D A,-WIB) might help clarifying the origin of distinct A, species from different tissues, cell types, or intracellular pools as well as their amyloidogenicity. It might further help identifying plasma A, species suitable as biomarkers for the diagnosis of Alzheimer's disease (AD). [source] | |||||||||||||