Early increases in soluble amyloid-β levels coincide with cholinergic degeneration in 3xTg-AD mice.

Accumulation of amyloid-β peptides (Aβ) and cholinergic degeneration are hallmarks of Alzheimer's disease (AD). In a triple transgenic mouse model of AD (3xTg-AD), soluble Aβ42 levels were detected in the septum by 2 months of age, reaching their highest levels at 3-6 months and decreasing at 12 months. Deficits in the number of septal cholinergic neurons and the length of hippocampal cholinergic axons were observed starting at 4 months in 3xTg-AD mice.

Amyloid-beta fibrillogenesis: structural insight and therapeutic intervention.

Structural insight into the conformational changes associated with aggregation and assembly of fibrils has provided a number of targets for therapeutic intervention. Solid-state NMR, hydrogen/deuterium exchange and mutagenesis strategies have been used to probe the secondary and tertiary structure of amyloid fibrils and key intermediates. Rational design of peptide inhibitors directed against key residues important for aggregation and stabilization of fibrils has demonstrated effectiveness at inhibiting fibrillogenesis.

Reduced oligomeric and vascular amyloid-beta following immunization of TgCRND8 mice with an Alzheimer's DNA vaccine.

Immunization with amyloid-beta (Abeta) peptide reduces amyloid load in animal studies and in humans; however clinical trials resulted in the development of a pro-inflammatory cellular response to Abeta. Apoptosis has been employed to stimulate humoral and Th2-biased cellular immune responses. Thus, we sought to investigate whether immunization using a DNA vaccine encoding Abeta in conjunction with an attenuated caspase generates therapeutically effective antibodies.

Vaccine development for Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of age-related cognitive decline. Both active and passive immunization paradigms have illustrated the potential to prevent and reverse established AD pathology in transgenic and non-transgenic animal models of AD. Follow-up studies have shown that changes in amyloid burden observed with immunization could rescue cognitive deficits in both young and aged mice.

New therapeutic approaches for Alzheimer's disease.

Extract: By undergoing a slight change in shape the normally innocuous peptide, amyloid-beta (A-beta) self-assembles forming aggregates, which are toxic to cells and induce a myriad of changes in the brain. It is now thought that the generation of these toxic species is an initial and necessary step in the pathogenic process underlying Alzheimer's disease (AD). The amyloid cascade hypothesis has led to the rational design of anti-amyloid therapeutics, which holds promise for the treatment and prevention of AD.

Regulation of Indian hedgehog mRNA levels in chondrocytic cells by ERK1/2 and p38 mitogen-activated protein kinases.

Indian hedgehog (Ihh) is produced by growth plate pre-hypertrophic chondrocytes, and is an important regulator of endochondral ossification. However, little is known about the regulation of Ihh in chondrocytes. We have examined the role of integrins and mitogen-activated protein (MAP) kinases in Ihh mRNA regulation in CFK-2 chondrocytic cells.