The Possibility of an Infectious Etiology of Alzheimer Disease.

Over the past three decades, there has been constant postulation regarding the infectious etiology of Alzheimer disease (AD), which in turn suggests the vital role of various infectious agents in AD-associated inflammatory pathways. Recent findings indicate anti-microbial properties of Aβ, and suggest that Aβ production and deposition in AD might be induced by infectious agents. Several types of spirochetes have been associated to dementia, cortical atrophy, and pathological and biological hallmarks of AD.

Classification (Agonist/Antagonist) and Regression "Structure-Activity" Models of Drug Interaction with 5-HT6.

Introduction: One promising target for novel psychotropic drugs is the 5-HT6 receptor, GProtein- Coupled Receptor (GPCR) family, displaying seven transmembrane domains. There is considerable interest in how both 5-HT6 receptor agonist and antagonist compounds can have marked procognitive effects.

Methods: An exact structure of the 5-HT6 receptor is not available, so application of powerful methods of (Q)SAR and molecular modelling, which play an essential role in modern drug design, are currently limited to structure-based homology models.

Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease.

Alzheimer's disease (AD) is a slowly progressive, neurodegenerative disorder of uncertain etiology. According to the amyloid cascade hypothesis, accumulation of non-soluble amyloid β peptides (Aβ) in the Central Nervous System (CNS) is the primary cause initiating a pathogenic cascade leading to the complex multilayered pathology and clinical manifestation of the disease. It is, therefore, not surprising that the search for mechanisms underlying cognitive changes observed in AD has focused exclusively on the brain and Aβ-inducing synaptic and dendritic loss, oxidative stress, and neuronal death.

Implications of farnesyltransferase and its inhibitors as a promising strategy for cancer therapy.

Ras proteins have been reported to play key role in oncologic diseases. Ras proteins are associated with cellular membranes for its carcinogenic activities through post-translational modifications, including farnesylation. Farnesyltransferase is responsible for a type of Ras membrane targeting, which leads to cancer origin and progression.

Portacaval shunting causes differential mitochondrial superoxide production in brain regions.

The portacaval shunting (PCS) prevents portal hypertension and recurrent bleeding of esophageal varices. On the other hand, it can induce chronic hyperammonemia and is considered to be the best model of mild hepatic encephalopathy (HE). Pathogenic mechanisms of HE and dysfunction of the brain in hyperammonemia are not fully elucidated, but it was originally suggested that the pathogenetic defect causes destruction of antioxidant defense which leads to an increase in the production of reactive oxygen species (ROS) and the occurrence of oxidative stress.

Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases.

Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity.

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia.

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis.

Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents.

Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments.

Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders.

In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain.

Relationship between chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes and Alzheimer disease.

Alzheimer disease (AD) is one of the most common neurodegenerative disorders widely occurring among the elderly. The pathogenic mechanisms involved in the development of this disease are still unknown. In AD, in addition to brain, a number of peripheral tissues and cells are affected, including erythrocytes.

Prophylactic Admission of an In Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanoma Antigenic Peptides Activates Anti-Melanoma Responses in Mice.

Tumor-derived autologous antigenic peptides when bound to endogenous 70 kDa family heat shock proteins (HSP70) are able to induce effective T-cell responses against tumors. However, efficacy of HSPbased vaccines in clinical practical stand point still has a number of certain limitations including an activation of immune responses against alien non-human HSPs. In this study we reconstructed the complexes of human recombinant HSPs70 (human recombinant HSP70A1B and HSC70 mixture; hrHSPs70) with antigenic lowweight peptides derived from mice B16F10 melanoma cell lysate (PepMCL) in vitro and investigated the prophylactic potential of these complexes to activate anti-tumor immunity in melanoma mouse model.

Beyond mitochondria, what would be the energy source of the cell?

Currently, cell biology is based on glucose as the main source of energy. Cellular bioenergetic pathways have become unnecessarily complex in their eagerness to explain that how the cell is able to generate and use energy from the oxidation of glucose, where mitochondria play an important role through oxidative phosphorylation. During a descriptive study about the three leading causes of blindness in the world, the ability of melanin to transform light energy into chemical energy through the dissociation of water molecule was unraveled.

Pathogenesis of Alzheimer disease: role of oxidative stress, amyloid-β peptides, systemic ammonia and erythrocyte energy metabolism.

Aβ exerts prooxidant or antioxidant effects based on the metal ion concentrations that it sequesters from the cytosol; at low metal ion concentrations, it is an antioxidant, whereas at relatively higher concentration it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely on the amyloid-β clearance should be re-examined in light of the vast accumulating evidence that increased oxidative stress in the human brains is the key causative factor for AD. Accumulating evidence indicates that the reduced brain glucose availability and brain hypoxia, due to the relatively lower concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased concentration of endogenous ammonia, a potential neurotoxin in the AD brains.