An altered cell-specific subcellular distribution of translesion synthesis DNA polymerase kappa (POLK) in aging neurons.

Genomic stability is critical for cellular function, however, in the central nervous system highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases.

The protective effect of early dietary fat consumption on Alzheimer's disease-related pathology and cognitive function in mice.

Introduction: It has been suggested that obesity may influence Alzheimer's disease (AD) pathogenesis, yet the numerous publications on this topic have inconsistent results and conclusions.

Methods: Our study examined the effect of varying the timing of high-fat diet (HFD) consumption on AD-related pathology and cognition in transgenic Tg6799 AD mice.

Results: HFD feeding starting at or before 3 months of age, prior to severe AD pathology, had protective effects in AD mice: reduced extracellular amyloid beta (Aβ) deposition, decreased fibrinogen extravasation into the brain parenchyma, and improved cognitive function.

Antioxidant and Cholinesterase Inhibitory Activities of Ethyl Acetate Extract of : Cell-free and Studies.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and impaired cognitive function. Cholinergic enzyme deficiency and oxidative stress are the two major factors implicated in the pathogenesis of AD. The symptomatic treatment, as of now, is the use of cholinesterase inhibitors toward cholinergic "downturn.

Resveratrol Intervenes Cholesterol- and Isoprenoid-Mediated Amyloidogenic Processing of AβPP in Familial Alzheimer's Disease.

Deterioration of cholesterol metabolism has recently been a frontier subject of investigation in the field of Alzheimer's disease (AD). Though amyloid-β protein precursor (AβPP) primes the pathological cascade, changes in cholesterol levels and its intermediates, geranyl geranyl pyrophosphate and farnesyl pyrophosphate, is expected to have a different consequence on AβPP processing and amyloid-β (Aβ) generation. However, the use of statins (HMG-COA reductase inhibitor) has been widely implicated in slowing down the pathogenic progression of AD, while the epidemiological reports on its biological effect remains controversial.

High throughput virtual screening and E-pharmacophore filtering in the discovery of new BACE-1 inhibitors.

Alzheimer's disease is a progressive neurodegenerative disorder, which is characterized by amyloid β peptide deposition in the brain. Aβ peptide, the major component of amyloid plaques is generated by the sequential processing of a larger protein called amyloid Precursor Protein by β-amyloid cleaving enzyme (BACE-1). In this study, we appllied computer assisted methodology unifying molecular docking and pharmacophore filtering to identify potent inhibitors against BACE-1.