Alzheimer Disease Peptides Products

Beta Amyloid Peptides for Alzheimer's Diseases

As neurodegenerative diseases have become more common in aging population, finding tgreatments or cures has become a major focus of reseaerchers worldwide.  These disease affect the central nervous system and are chareacterized by loss of specific neuronal populations, and quite often intraneuronal, as well as extracellular accumulation of fibrillary materials. Most neurodegenerative diseases of the brain such as Alzheimer’s disease are caused by accumulation of protein in brain. In an Alzheimer’s patient’s brain, amyloid beta peptide (Aβ) aggregates to form amyloid plaques while tau protein aggregates to form neurofibrillary tangles in the neurons. These two components have been the center of studies involving pathological pathway in neurodegenerative diseases including Alzheimer and Parkinson disease.¹

Amyloid beta peptides

Amyloid beta peptides are derived from proteolytic processing of amyloid precursor protein (APP) by β and γ secretases. This post translation modification results in Aβ (1-42) and (1-40), the most studied fragments of β-amyloid peptides.² Aβ(1-42) fragment has been proposed the form amyloid senile plaques while the soluble A(1-40) primarily forms fibrils.³

In order to understand the mechanism of plaque formation, solution structure of Aβ(1-42) using NMR studies have been elucidated and have shown that the N-terminus residues 1 -10 are unstructured while residues 11-42 form β-strand-turn-β-strand structure (Figure 1B).⁵  Both Aβ(1-42) and Aβ(1-40) have been shown to form similar beta strand-turn-beta strand structure.^6-7

Tau Proteins

Tau is a highly unstructured and soluble microtubule-associated protein. Its function in the brain is to regulate microtubule dynamics, axonal transport and neurite outgrowth in neurons.⁸ In Alzheimer patients, Tau protein is abnormally phosphorylated, this observation strongly suggested the key role of tau in neurofibrillary tangles formation, a condition associated with many neurodegenerative diseases.^9-10 Other post translational modification found in tau protein of an Alzheimer patient include; glycation, transglutamylation and caspase cleavage.¹¹ Tau, a 441 amino acid residues protein has 40 serine and threonine residues which are possible phosphorylation sites. Although this hyperphosphorylation is found in the brain of Alzheimer patients, not all the phosphorylated sites are associated with the disease since phosphorylated tau protein has been isolated in healthy brain. Despite the extensive research done on neurofibrillary tangles formed by phosphorylate tau protein, limited information is available regarding the specific phosphorylation site relevant neurodegenerative disease. Anti-tau antibodies raised against phosphorylated tau protein epitopes, have been utilized in immunodiagnostics of tau neurofibrillary tangles.¹² As such, researchers have indicated that Tau immunotherapy can be a good target for Alzheimer disease therapy as well as Taupathie.β

References:

1. Suh Y-H., and Checler F. Pharmacol. Rev., 2002, 54, 469-525
2. Ahmed et al., Nat. Struct. & Mol. Biol. 2009, 17, 561-567
3. Luhr et al., PNAS 2005 ,102, 17342-17347
4. Olofsson et al., J. Biol Chem. 2006 281, 477-483
5. Paravastua et al., PNAS 2008 ,105 18349-18354
6. Marshall and Serpell, The Open Biology Journal, 2009, 2, 185-192
7. Schmidt et al., PNAS 2009, 106, 19813-19818
8. Chambraud et al., PNAS 2010 ,107, 2658-2663
9. Baumann et al., FEBS 1993,  417-424
10. Rapoport et al., PNAS 2002, 99, 6364-6369
11. Pickhardt et al., Current Alzheimer Research 2005, 2, 219-226
12. Taniguchi et al., FEBS 2005,  1399-1404