Fruitless Wolfberry-Sprout Extract Rescued Cognitive Deficits and Attenuated Neuropathology in Alzheimer's Disease Transgenic Mice.

Background: Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aβ leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aβ levels and inhibiting Aβ-induced neurotoxicity are feasible therapeutic strategies for AD treatment.

A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice.

Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into β-amyloid (Aβ); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects.

Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines.

Alzheimer's disease (AD) is a complex, multi-factorial neurodegenerative disease. The aggregation of soluble β-amyloid (Aβ) into fibrillar deposits is a pathological hallmark of AD. The Aβ aggregate-induced neurotoxicity, inflammatory reactions, oxidative stress, and nitric oxide (NO) generation are strongly linked to the etiology of AD.

Conformation-dependent scFv antibodies specifically recognize the oligomers assembled from various amyloids and show colocalization of amyloid fibrils with oligomers in patients with amyloidoses.

Increasing evidence indicates that amyloid aggregates, including oligomers, protofibrils or fibrils, are pivotal toxins in the pathogenesis of many amyloidoses such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, prion-related diseases, type 2 diabetes and hereditary renal amyloidosis. Various oligomers assembled from different amyloid proteins share common structures and epitopes. Here we present data indicating that two oligomer-specific single chain variable fragment (scFv) antibodies isolated from a naïve human scFv library could conformation-dependently recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ1-40, prion peptide 106-126 and lysozyme, and fibrils from lysozyme.

α-Tocopherol quinone inhibits β-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines.

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disease. The aggregation of beta-amyloid (Aβ) into extracellular fibrillar deposition is a pathological hallmark of AD. The Aβ aggregate-induced neurotoxicity, inflammatory reactions and oxidative stress are linked strongly to the etiology of AD.

Diverse ecdysterones show different effects on amyloid-β42 aggregation but all uniformly inhibit amyloid-β42-induced cytotoxicity.

Amyloid-β (Aβ) plays a pivotal role in Alzheimer's disease (AD) pathogenesis and in toxic mechanisms such as oxidative stress, mitochondrial dysfunction, calcium turbulence, and apoptosis induction. Therefore, interfering with Aβ aggregation has long been one of the most promising strategies for AD treatment. Ecdysterones (ECRs) are steroidal hormones in insects and terrestrial plants that have high structural diversity and multiple beneficial pharmacological activities.

Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity.

Smaller, soluble oligomers of beta-amyloid (Abeta) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of Abeta oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against Abeta neurotoxicity.

Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation.

Beta-amyloid (Abeta) aggregation has been strongly associated with the neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's disease (AD). Inhibition of Abeta assembly, destabilization of preformed Abeta aggregates and attenuation of the cytotoxicity of Abeta oligomers and fibrils could be valuable therapeutics of patients with AD. Recent studies suggested that moderate consumption of red wine and intake of dietary polyphenols, such as resveratrol, may benefit AD phenotypes in animal models and reduce the relative risk for AD clinical dementia.

Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers.

Increasing evidence indicates that beta-amyloid (Abeta) oligomers rather than monomers or fibrils are the major toxic agents that specifically inhibit synaptic plasticity and long-term potentiation (LTP) in Alzheimer's disease (AD). Neutralization of Abeta oligomeric toxicity was found to reverse memory deficits. Here, we report four single-chain variable fragment (scFv) antibodies isolated from the naive human scFv library by phage display that specifically recognized Abeta oligomers but not monomers and fibrils.