Amyloid Precursor Protein (APP) is a type I transmembrane protein and occurs in three isoforms, APP695, APP751, and APP770. APP contains a signal sequence, a large N-terminus extracellular region, a single transmembrane region and a cytoplasmic C-terminus region. APP is proteolytically cleaved by caspases (3,6,8,9) and secretases (alpha, beta, gamma). With respect to isoform APP770, caspase 6 cleaves at amino acid 672 and caspases 3, 6, 8, 9 cleave APP at amino acid 739. Caspase cleavage at amino acid 739 results in the release of a C-terminus fragment (CTF) of 31 amino acids named C31 (Nature Medicine, 6: 397-404, 2000). The C31 fragment contains the GYENPTY motif that has been shown to interact with many cytoplasmic and is required for enhancing beta amyloid toxicity. The C31 peptide may play a critical role in apoptosis and be involved in neuronal death associated with Alzheimer’s disease (FASEB J, 20: E546-E555, 2006, PNAS, 103: 7130-7135, 2006). Caspase 6 cleavage at amino acid 672 may increase beta amyloid peptide generation and lead to an increase in early events in Alzheimer’s disease (Am J Pathol, 170: 1200-1209, 2007).

Beta Amyloids are generated as cleavage products from the action of proteases on Amyloid Precursor Protein (APP). Beta and gamma secretase, the two proteases that cleave APP at the N and C terminus, are responsible for the generation of beta amyloid 1-40 and 1-42. Alhpa secretase cleaves APP within the the beta amyloid domain and precludes the generation of 1-40 or 1-42 (Proc Natl Acad Sci, 96; 3922-3927, 1999, J Clinical Investigation, 108; 1243-1246, 2001, J Clinical Investigation, 113; 1384-1387, 2004, J Biol Chem, 279; 18146-18156, 2004). FRET-based peptide substrates are now offered to study beta secretase and alpha secretase activity (catalog # 20-1029 and 20-1032). Beta amyloids 25-35, 1-28 Gln11, 1-40, 1-42 and 1-43 are available to study amnesia, aggregation and neurotoxicity both in vitro and in vivo (Proc Natl Acad Sci, 88; 3363-3366, 1991, Eur J Pharmacol, 319; 1-4, 1997, Eur J Pharmacol, 506; 55-61, 2004, American J Pathology, 165; 937-948, 2004) . Additional amyloid peptides have been added to study the interaction of beta amyloid with apolipoprotein E (apoE). The binding site of apoE on beta amyloid corresponds to amino acid residues 12 to 28. Studies show that substitution of valine18 with proline18 blocks binding of beta amyloid to apoE and reduces the rate of new plaque formation in mice (American Journal of Pathology, 165: 937-948, 2004, PNAS, 103: 18787-18792, 2006). Catalog peptides 20-1011 (beta amyloid 17-21, P18D21) and catalog peptide 20-1014 (beta amyloid 12-21, P18) and the myristoylated sequences are now available for research studies.

Neuronal death suppressing peptides for Alzheimer’s Disease and Amyotrophic Lateral Sclerosis have been identified and studied. Humanin, a 24 amino acid neuroprotective peptide, and colivelin, a 26 amino acid peptide composed of activity-dependent neurotrophic factor (ADNF) fused to a 17 amino acid derivative of Humanin, have shown to completely protect neuronal death in mouse models for Alzheimer’s Disease and Amyotrophic Lateral Sclerosis (J Neuroscience Res., 78, 542-552, 2004,Invest Ophthalmol Vis Sci, 46;933-938, 2005, J Neuroscience, 25; 10252-10261, 2005, CNS Drug Reviews, 12; 113-122, 2006). Catalog peptides are now available for Humanin (20-1033), Colivelin (20-1034), ADNF-9 (20-1035, activity dependent neurotrophic factor), and NAP (20-1037, activity dependent neuroprotective protein).