Efficient access to highly pure β-amyloid peptide by optimized solid-phase synthesis

Choi, Ji Won; Kim, Hye Yun; Jeon, Mijin; Kim, Dong Jin; Kim, Young Soo

doi:10.3109/13506129.2012.700287

Cited by 25 publications

(28 citation statements)

References 30 publications

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“…Aβ42 peptides were synthesized by following the DMSO-incorporated Fmoc solid phase peptide synthesis (SPPS) protocol 40 . Necrostatin-1 (Nec-1) and thioflavin S (ThS) were bought from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

A small molecule Nec-1 directly induces amyloid clearance in the brains of aged APP/PS1 mice

Yang

Shin

et al. 2019

Sci Rep

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the formation of toxic amyloid-β (Aβ) oligomers and plaques. Considering that Aβ misfolding and aggregation precedes the progressive development of cognitive impairment in AD, investigating a therapeutic means by clearance of pre-existing Aβ aggregates shows promise as a viable disease-modifying treatment. Here, we report that a small molecule, necrostatin-1 (Nec-1), reduces Aβ aggregates back to non-toxic monomers in vitro and in vivo. Intravenous administration of Nec-1 reduced the levels of Aβ plaques in the brains of aged APP/PS1 double transgenic mice. In addition, Nec-1 exhibited therapeutic effects against Aβ aggregates by inhibiting Aβ-induced brain cell death in neuronal and microglial cell lines. Nec-1 also showed anti-apoptotic and anti-necroptotic effects in the cortex of aged APP/PS1 mice by reducing levels of phosphorylated-RIPK3 and Bax and increasing the levels of Bcl-2. According to our data in vitro and in silico, the methyl group of the amine in the 2-thioxo-4-imidazolidinone is the key moiety of Nec-1 that directs its activity against aggregated Aβ. Given that the accumulation of Aβ aggregates is an important hallmark of AD, our studies provide strong evidence that Nec-1 may serve a key role in the development of AD treatment.

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Section: Methodsmentioning

confidence: 99%

A small molecule Nec-1 directly induces amyloid clearance in the brains of aged APP/PS1 mice

Yang

Shin

et al. 2019

Sci Rep

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“…Cold anhydrous ether (stored in −20°C) was added and centrifuged at 3000 rpm for 10 minutes twice. Finally, precipitated white powder was isolated, dissolved in 50% acetonitrile, lyophilized and purified using reverse-phase HPLC as previously reported 22 .…”

Section: Methodsmentioning

confidence: 99%

Correlations of amyloid-β concentrations between CSF and plasma in acute Alzheimer mouse model

Cho

Kim

Lee

et al. 2014

Sci Rep

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Amyloid-β (Aβ) is one of the few neuropathological biomarkers associated with transporters of the blood-brain barrier (BBB). Despite the well-characterized clinical indication of decreasing Aβ levels in the cerebrospinal fluid (CSF) during the development of Alzheimer's disease (AD), the link between the alternation of Aβ level in the blood and the progress of the disorder is still controversial. Here, we report a direct correlation of Aβ(1–42) levels between CSF and plasma in AD mouse model. We injected monomeric Aβ(1–42) directly into the intracerebroventricular (ICV) region of normal adult mouse brains to induce AD-like phenotypes. Using sandwich enzyme-linked immunosorbent assays, we observed proportional elevation of Aβ(1–42) levels in both CSF and plasma in a dose-dependent manner. Our findings that plasma Aβ(1–42) reflects the condition of CSF Aβ(1–42) warrant further investigation as a biomarker for the blood diagnosis of AD.

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“…1. Treat the Aβ peptides, derived through chemical synthesis 5 or from commercial sources, with pre-chilled 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) to dissolve any aggregates and to make the peptides homogenous 6 . 1.…”

Section: Aβ Peptide Preparationmentioning

confidence: 99%

Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits

Kim

Lee

Chung

et al. 2016

JoVE

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Amyloid-β (Aβ) is a major pathological mediator of both familial and sporadic Alzheimer's disease (AD). In the brains of AD patients, progressive accumulation of Aβ oligomers and plaques is observed. Such Aβ abnormalities are believed to block long-term potentiation, impair synaptic function, and induce cognitive deficits. Clinical and experimental evidences have revealed that the acute increase of Aβ levels in the brain allows development of Alzheimer-like phenotypes. Hence, a detailed protocol describing how to acutely generate an AD mouse model via the intracerebroventricular (ICV) injection of Aβ is necessary in many cases. In this protocol, the steps of the experiment with an Aβ-injected mouse are included, from the preparation of peptides to the testing of behavioral abnormalities. The process of preparing the tools and animal subjects before the injection, of injecting the Aβ into the mouse brain via ICV injection, and of assessing the degree of cognitive impairment are easily explained throughout the protocol, with an emphasis on tips for effective ICV injection of Aβ. By mimicking certain aspects of AD with a designated injection of Aβ, researchers can bypass the aging process and focus on the downstream pathology of Aβ abnormalities.

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Efficient access to highly pure β-amyloid peptide by optimized solid-phase synthesis

Cited by 25 publications

References 30 publications

A small molecule Nec-1 directly induces amyloid clearance in the brains of aged APP/PS1 mice

A small molecule Nec-1 directly induces amyloid clearance in the brains of aged APP/PS1 mice

Correlations of amyloid-β concentrations between CSF and plasma in acute Alzheimer mouse model

Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits

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Efficient access to highly pure β-amyloid peptide by optimized solid-phase synthesis

Cited by 25 publications

References 30 publications

A small molecule Nec-1 directly induces amyloid clearance in the brains of aged APP/PS1 mice

A small molecule Nec-1 directly induces amyloid clearance in the brains of aged APP/PS1 mice

Correlations of amyloid-β concentrations between CSF and plasma in acute Alzheimer mouse model

Intracerebroventricular Injection of Amyloid-&#946; Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits

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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits