Peptides in Alzheimer’s Disease

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Neurodegenerative Disease Peptides

Overview

Alzheimer's Disease (AD) affects 36 million people worldwide and is characterized by two types of hallmark aggregates: Extracellular aggregates formed by beta-amyloid peptides and intracellular neurofibrillary tangles (NFTs) consisting of Tau proteins. AD is the leading cause of dementia. Afflicted patients suffer from progressive memory loss, as well as loss of other cognitive functions.

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The role of Tau proteins in Alzheimer's Disease

Beta-amyloid peptides compose the amyloid plaques of AD and are the result of improper processing of the amyloid precursor protein (APP). Secreted by all neurons, APPs in AD patients undergo two abnormal cleavages resulting in the creation of toxic C-terminal beta-amyloid peptides. First, APP (770 aa in length) is cleaved by the enzyme beta-secretase, resulting in a 99 aa long peptide fragment. This fragment is then cleaved by another enzyme, gamma-secretase, resulting in 38 to 43 aa long beta-amyloid peptides. Of these peptides, beta-amyloid (1-42) exhibits the most amyloidogenic properties and is the principal component of amyloid plaques. Beta-amyloid peptides self-assemble into stacks of ordered parallel beta sheets as they form the plaques of AD.

The genetic origin of beta-amyloid formation stems from mutations in the APP gene, or one of two versions of the presenilin genes (PSEN1 or PSEN2) that result in the overproduction of APP. Duplication of the APP gene results in excess APP production as well. Increased amounts of beta-amyloid correlate with AD progression.

Beta-amyloid peptides in Alzheimer's Disease fundamental and therapeutic research

Beta-amyloid peptides are useful for numerous research projects including:
1. The study of beta-amyloid peptide self-assembly mechanisms.
2. The study of interactions between beta-amyloid and other proteins or peptides involved in amyloid plaque assembly.
3. The identification of drug molecules that inhibit beta-amyloid peptide self-assembly.
4. The development of beta-amyloid peptides as vaccines that result in the clearing of amyloid plaques by the immune system.

Beta-amyloid Peptide Research Toolbox

Click beta-amyloid peptide synthesis

Specially synthesized soluble beta-amyloid peptide that can be restored to its insoluble, native form simply by a change in pH (See tab below).

Custom beta-amyloid peptide synthesis

GenScript's PepPower™ synthesis platform can synthesize any beta-amyloid peptide sequence or modified sequence you design regardless of hydrophobicity or complexity.

Custom peptide solubility testing

Personalized solubility test and report prepared by our peptide synthesis experts to help you maximize dissolution of your custom peptide order (See tab below).

Beta-amyloid product peptides

Over 50 beta-amyloid peptide fragments ready for delivery.

View peer-reviewed beta-amyloid research publications that cite GenScript Custom Peptide Synthesis Services

1.Wu H, Zhang F, Williamson N, Jian J, Zhang L, Liang Z, Wang J, An L, Tunnacliffe A, Zheng Y. (2014) Effects of Secondary Metabolite Extract from Phomopsis occulta on β-Amyloid Aggregation.

PLoS One. 9(90): e109438.

2.Syad AN, Devi KP. (2015) Assessment of anti-amyloidogenic activity of marine red alga G. acerosa against Alzheimer's beta-amyloid peptide 25-35.

Neurol Res. 37(1): 14-22.

3.Mirza Z, Pillai VG, Zhong WZ. (2014) Structure of N-Terminal Sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-Peptide with Phospholipase A2 from Venom of Andaman Cobra Sub-Species Naja naja sagittifera at 2.0 Å Resolution.

Int J Mol Sci. 15(3): 4221-36.

4.Vargas LM, Leal N, Estrada LD, GonzÁlez A, Serrano F, Araya K, Gysling K, Inestrosa NC, Pasquale EB, Alvarez AR. (2014) EphA4 Activation of c-Abl Mediates Synaptic Loss and LTP Blockade Caused by Amyloid-β Oligomers.

PLoS One. 9(3): e92309.

5.Y Hu, HQ Zheng, B Su, M Hernandez, JR Kim. (2012) Modulation of beta-amyloid aggregation by engineering the sequence connecting beta-strand forming domains.

Biochim Biophys Acta. 1824(10): 1069-79.

Click Beta-amyloid Peptide Synthesis
Solubility Testing

Click peptide synthesis is a powerful tool for making naturally insoluble beta-amyloid peptides soluble. The soluble beta-amyloid peptide, (called a click beta-amyloid peptide) is synthesized using a special peptide synthesis method called O-acyl synthesis. This method is used to introduce a strategically placed O-acyl bond in place of a native N-acyl bond in the natural beta-amyloid peptide. The introduction of the O-acyl bond in the newly formed click beta-amyloid peptide enhances the peptide's solubility and decreases self-assembly.

Upon a pH change, the soluble click beta-amyloid peptide returns to its native, insoluble form. The ability to control the solubility of the beta-amyloid peptide allows for the design of assays to study self-assembly mechanics and the identification of beta-amyloid aggregation inhibitors.

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The Origins of Tau Proteins

The physiological role of Tau involves assisting the assembly of tubulin into microtubules, which are key to neuronal development and support. Binding of tubulin to Tau is regulated by phosphorylation and dephosphorylation by kinases and phosphatases, respectively. Hyperphosphorylation of Tau results in aberrant tubulin binding and the subsequent unorganized assembly of Tau proteins into the characteristic neurofibrillary tangles (NFTs) of AD.