关于 "Cytoskeleton & Motor Proteins" 的结果111+ 个结果

与内盐相比，Aβ42 的盐酸盐在 pH 7.4 时更容易聚集。

Experiments using sub-peptides of Aβ42 revealed that the epitope identified by the antibody A8, as described by Ying and coworkers, lies within the 1-6 region of Aβ. The antibody displays high affinity for soluble Aβ42 oligomers in the molecular weight range of 16.5-25 kDa, and detected target antigen in brain sections from senescence-accelerated SAMP 8 mice.

Aβ 2-42 could be a biomarker for differentiating AD from other degenerative dementias, such as frontotemporal dementias (FTD). The peptide promotes phagocytosis by macrophages.

The N-terminally truncated Aβ42 may be formed in increased amounts as AD progresses. Aβ 3-42 is the precursor of the Pyr-peptide. (Pyr³)-Aβ 3-42 positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate.

Aβ 4-42 could be one of the earliest and most prominent Aβ species deposited in AD brain. Sequencing of amyloid plaque cores showed that 64% of the isolated Aβ had a phenylalanine at its N-terminus, and indeed, IP/MS experiments identified Aβ 4-42 as a major Aβ species in AD patients. Additionally, Aβ 4-42 was found to be a component of cotton wool plaques in familial AD patients with the V261I PS1 mutation. Aβ 4-42 was discovered as well in amyloid deposits from vascular dementia and familial Danish dementia patients. These observations indicate that Aβ 4-42 may contribute to the development of multiple CNS diseases.

The Dutch mutation (E22Q) of amyloid β-peptide aggregates more readily than the wild-type peptide and the resulting fibrils show increased neurotoxicity. The mutant peptide E22Q induced apoptosis of cerebral endothelial cells at a concentration of 25 μm, whereas WT Aβ 1-40 and the Italian mutant E22K (H-6698) showed no effect.

The Dutch mutation (E22Q) aggregates more readily than the wild-type sequence. The resulting fibrils show increased neurotoxicity.

Contrary to β-amyloid peptides mutated at position 22 (Dutch, Italian, Arctic mutants) the Flemish mutation (A21G) shows a decreased tendency to aggregate and a reduced neurotoxicity. In the studies of Betts and Tsubuki, A21G was degraded significantly more slowly by neprilysin than the wild-type Aβ 1-40 and the E22 mutants. The relative resistance to proteolytic degradation may account for the pathogenicity of the Aβ mutant.

The Flemish mutation (A21G) shows a decreased tendency to aggregate and a reduced neurotoxicity. A21G is pathogenic as it is degraded significantly more slowly by neprilysin than WT Abeta42.

The highly neurotoxic arctic mutant (E22G) of Aβ has been used to study the mechanisms underlying the formation of soluble and insoluble β-amyloid aggregates. As the wild-type Aβ, the arctic mutant preferably assembles in the presence of GM1 ganglioside.

The arctic mutant of amyloid β peptide 1-42, in which Glu²² is substituted by Gly, is distinctly more amyloidogenic than the wild-type Aβ 1-42.

KKLVFFA contains the KLVFF sequence, which is the minimum sequence binding the full-length amyloid β-protein. It showed improved water solubility compared with KLVFF (H-3682). It can be used as a labeled probe for screening defined sequences in the full-length amyloid β-protein.

The Italian mutation of β-amyloid 1-40 (E22K) aggregates more rapidly than the wild-type sequence 1-40. It showed increased neurotoxicity, which (according to a solid-phase NMR-study of Masuda et al.) may be due to the salt bridge formed between Lys²² and Asp²³ in the minor conformer. As the Arctic, Flemish, and Dutch mutants, the Italian mutant is degraded considerably more slowly than wild-type Aβ by neprilysin.

The Italian mutation (E22K) aggregates more rapidly than the wild-type sequence.

The reactive thioether of Met³? is crucial for the activity of Aβ 1-40 and Aβ 1-42. Due to the replacement of Met by inert Nle, M35Nle Aβ 1-40 was no longer toxic to cultured hippocampal neurons and had little effect on the level of protein carbonyl residues. The Nle peptide showed the same propensity to aggregate, whereas sulfoxide formation hindered the required conformational transition from random coil to β-sheet.

The thioether of Met³? plays a critical role in the oxidative stress induced by Aβ 1-42 and its neurotoxicity. The norleucine analog Aβ 1-42 M35Nle forms fibrils morphologically indistinguishable from the ones of the native sequence though lacking their neurotoxicity.

pEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV, the N-terminally truncated isoform of the amyloid β-protein (Aβ) beginning with a pyroglutamate (Pyr) residue at position 11 was used in experiments studying the generality of fibrillogenesis-related helix formation. Comparing the fibrillogenesis kinetics of many of the most important clinically relevant amyloid β-protein alloforms it could be observed that among these peptides (Pyr¹¹)-amyloid β-protein (11-40) exhibited the greatest retardation of fibrillization rate.

The pyroglutamate-modified amyloid-β peptides derived from Aβ40 (H-7422) and Aβ42 (H-4796) have gained considerable attention as potential key participants in the pathology of Alzheimer's disease (AD) due to their abundance in AD brain, high aggregation propensity, stability, and cellular toxicity. Aβ40 and 42 can be N-terminally truncated by action of cathepsin B. The cyclization of Glu³ is catalyzed by glutaminyl cyclase. Hence, inhibition of these enzymes could be a therapeutic approach to AD.

(Pyr³)-Amyloid β-Protein (3-42) was found to be the predominant amyloid β-peptide structure deposited in human brain of Alzheimer's disease and Down's syndrome patients. Therefore, (Pyr³)-Aβ (3-42) is suggested to accumulate in the brain and to trigger the formation of insoluble amyloid β-peptide deposits. Nussbaum et al. studies the Prion-like behaviour and tau-dependent cytotoxicity of the truncated Aβ sequence.

A mutation very close to the β-secretase cleavage site of APP. The Icelandic mutation A2T of Aβ42 turned out to be less pathogenic than the native sequence. The precursor APP A673T was the first APP variant discovered in humans reducing the risk of Alzheimer's disease. A2T as well affects γ-secretase cleavage, the mutant was an inefficient substrate in a cell-based assay of the enzyme.

A mutation very close to the β-secretase cleavage site of APP (A673V). Contrary to the protective Icelandic mutation A2T, the recessive A2V mutation may increase the risk of Alzheimer's disease. Cantu et al. observed that APP A673V is associated with the early onset of AD-type dementia in homozygous individuals, whereas it has a protective effect in the heterozygous state.