Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques

AbstractWe analyzed an amino-terminal modification of β-amyloid (Aβ) peptide in brain, using anti-Aβ antibodies that distinguish distinct molecular species. Examination of cortical sections from 28 aged individuals with a wide range in senile plaque density revealed that a molecular species distinct from the standard Aβ is deposited in the brain in a dominant and differential manner. This modified Aβ peptide (AβN3(pE)) starts at the 3rd amino-terminal residue of the standard Aβ, glutamate, converted to pyroglutamate through intramolecular dehydration. Because plaques composed of AβN3(pE) are present in equivalent or greater densities than those composed of standard Aβ bearing the first aminoterminal residue (AβN1) and because deposition of the former species appears to precede deposition of the latter, as confirmed with specimens from Down's syndrome patients, the processes involved in AβN3(pE) production and retention may play an early and critical role in senile plaque formation

Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite

Cigarette smoke is associated to pathological weakening of bone tissue, being considered an important playmaker in conditions such as osteoporosis and periodontal bone loss. In addition, it is also associated with an increased risk of failure in bone regeneration strategies. The present work aimed to characterize the effects of nicotine on human osteoclastogenesis over a hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or presence of the osteoclastogenesis enhancers M-CSF and RANKL, and were further treated with nicotine levels representative of the concentrations observed in the plasma and saliva of smokers. It was observed that nicotine at low concentrations elicit an increase in osteoclast differentiation, but only in the presence of M-CSF and RANKL it was also able to significantly increase the resorbing ability of osteoclasts. A slight downregulation of NFkB pathway and an increase in the production of TNF-α and, particularly PGE2, were involved in the observed effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects, causing a decrease in cell density. In conclusion, nicotine at levels found in the plasma of the smokers, has the ability to act directly on osteoclast precursors, inducing its osteoclastogenic differentiation. The stimulatory behavior appears to be dependent on the stage of osteoclastic differentiation of the precursor cells, which means, in the absence of M-CSF and RANKL, it only favors the initial stages of osteoclast differentiation, while in the presence of the growth factors, a significant increase in their resorbing ability is also achieved.info:eu-repo/semantics/publishedVersio

Calcium-Activated Neutral Protease Quickly Converts α-Connectin to β-Connectin in Chicken Breast Muscle Myofibrils : COMMUNICATION : Biochemistry

Volume: 6Start Page: 797End Page: 80