[Arg6]-β-Amyloid (1-40), England mutation 是具有生物活性的肽,与多种家族性常染色体显性阿尔茨海默病相关。特别地,这种英国突变,即位于第6位的His被Arg所替换,已报告可提高寡聚体形成动力学,加速初级纤维的种子化过程。此类寡聚体对神经元培养细胞展现出较高毒性。
Pramlintide is a non-amyloidogenic analog of the antidiabetic peptide hormone amylin that contains proline residues substituted at positions 25, 28, and 29. It stimulates cAMP production in HEK293 cells expressing human amylin receptor 1a (AMY1a), AMY2a, and AMY3a (EC50s = 0.35, 22.9, and 0.89 nM, respectively). Pramlintide inhibits human islet amyloid polypeptide fibrilization in a concentration-dependent manner. In vivo, pramlintide (200 pg/kg) reduces brain levels of amyloid-β (1-40) and increases spontaneous alternation in the Y-maze in the Tg2576 transgenic mouse model of Alzheimer's disease.
Amyloid-β (1-8, A2V) is a truncated form of amyloid-β (Aβ) that contains a valine to alanine substitution at position 2 of the Aβ numbering convention (Aβ A2V), which corresponds to position 673 of the amyloid precursor protein (APP) numbering convention (APP A673V). An Aβ (1-40) (Aβ40) A2V peptide increases the production of Aβ and the rate and amount of amyloid fibril formation in vitro, effects that can be reduced by coincubation with wild-type Aβ40. Aβ40 and Aβ42 levels are increased in CHO cells expressing the Aβ A2V mutation and in fibroblasts derived from patients with the Aβ A2V mutation. As a homozygous mutation, Aβ A2V is correlated with Alzheimer's disease with distinctive pathological features, but disease does not develop in patients with a heterozygous Aβ A2V mutation.
Amyloid-β (25-35) (Aβ (25-35)) is an 11-residue fragment of the Aβ protein that retains the physical and biological characteristics of the full length peptide. It forms fibrils that react to thioflavin T and Congo red and are organized in a cross-β arrangement of β-strands similar to Aβ (1-40) and Aβ (1-42) fibrils. Aggregated Aβ (25-35) decreases the viability of rat adrenal PC12 cells. It also decreases the viability of primary rat cortical neurons at concentrations ranging from 1 nM to 30 μM. In vivo, intracerebral injection of Aβ (25-35) (20 nmol) in rats induces lesions of neuronal and tissue loss. Aggregated Aβ (25-35) administered intracerebroventricularly to rats induces learning and memory impairments in the Y-maze, novel object recognition, and contextual fear conditioning tests.
Glycerophosphorylethanolamine is an active phosphodiester metabolite of phosphatidylethanolamine.1,2It promotes aggregation of amyloid-β (1-40) (Aβ40)in vitro, and levels of glycerophosphorylethanolamine are elevated in postmortem brains isolated from patients with Alzheimer’s disease. 1.Klunk, W.E., Xu, C.J., McClure, R.J., et al.Aggregation of β-amyloid peptide is promoted by membrane phospholipid metabolites elevated in Alzheimer’s disease brainJ. Neurochem.69(1)266-272(1997) 2.Blusztajn, J.K., Lopez Gonzalez-Coviella, I., Logue, M., et al.Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer’s disease but not of Down’s syndrome patientsBrain Res.536(1-2)240-244(1990)