Enhanced Cleavage of Amyloid  Peptides in the Case in Injected Inflammatory Brain of Mice

Abstract

The excessive accumulation of Amyloid íŸ-Peptides (AíŸs) in the brain is the causative factor in all genetic as well as sporadic cases of Alzheimer's disease (AD). Two enzymes namely beta-Secretase and gamma-Secretase are involved in the defective cleavage of Amyloid Precursor Protein (APP) and the alpha-Secretase is involved in the normal processing. The core Protein of the Amyloid senile plaques within the brains of afflicted individuals contains Peptide of 39-43 residues, but mostly terminating with residues 40 and 42. The longer AíŸ₄₂ is more abundant in the Amyloid of the neuritic plaques while the shorter Peptides (AíŸ₄₀) found more in the vascular deposits. Factors that lead to the over expression of AíŸs are yet to be identified. In the present study, we have shown that the prolonged subcutaneous injection of casein, confirmed the presence of a fibrillary Protein deposits with Amyloid characteristics in chronic Inflammation and associated Systemic Amyloidosis, triggers about 20 times more Abeta accumulation in the mice Brain than that of the control mice and confirmed as well as quantified by RP-HPLC. From the Mass Spectroscopic analysis, we have shown the occurrence of a new type of proteolytic zeta cleavage fragment, a 1-54 residue Abeta in the mice Brain along with the Abeta Peptides.