Current Pharmaceutical Design - Volume 19, Issue 36, 2013

Sporadic Alzheimer’s disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and b Read More

Introduction of diffusion tensor imaging (DTI) in 1980 and its advancement in the last three decades offered the possibility to visualize and quantify changes in white matter. DTI allows the evaluation of the structural integrity in complex neurodegenerative diseases, such as Alzheimer’s disease (AD). Progressive disintegration of functional and structural neural network coordination contributes to the cognitive dysfunction in AD. T Read More

The pathophysiological mechanisms underlying normal aging and neurodegenerative disorders represent the focus of a bulk of recent research. Physiological brain aging is characterized by a progressive dysfunction and loss of synaptic contacts and neuronal abnormal apoptosis. Neural and synaptic redundancy as well as functional and structural plastic remodeling of brain networking promote maintenance of brain activity i Read More

Neuronal transmission and functional synapses require mitochondria, which are mainly involved in the generation of energy (ATP and NAD+), regulation of cell signaling and calcium homeostasis. Particularly intriguing is emerging data suggesting the relationship between mitochondria and neurotrophic factors that can act at the synaptic level promoting neuronal transmission and plasticity. On the other hand, disturbances i Read More

Schizophrenia is a major mental illness that is characterized by psychosis, apathy, social withdrawal and cognitive impairment. These abnormalities in patients results in impaired functioning in work, school, parenting, self-care, independent living, interpersonal relationships, and leisure. Although the search for the biological correlates of schizophrenia has met with limited success, new advances in genetics and pharmacology are Read More

Schizophrenia is a chronic, often disabling mental illness with a lifetime prevalence of ~1% worldwide, and 2-to-3 times higher mortality rates are reported in schizophrenia patients compared to the general population. Although research has been increasingly focusing on identifying novel diagnostic and treatment resources for this illness, the diagnosis of schizophrenia is still based on clinical criteria, which are subjectively Read More

The term “Autism Spectrum” is often used to describe disorders that are currently classified as Pervasive Developmental Disorders. These disorders are typically characterized by social deficits, communication difficulties, stereotyped or repetitive behaviors and/or cognitive delays or mental retardation; sometimes they present high comorbidity rates with epilepsy. Although these diagnoses share some common features, indi Read More

Neurosteroids play essential roles in the control of central nervous system functions during physiological and pathological conditions. Increasing evidences show gender differences in the pathogenesis and clinical manifestations of several neurodevelopmental conditions, including Autism Spectrum Disorders (ASD), possibly due to the action of sex hormones during critical periods of brain development. Furthermore, it is kn Read More

In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems Read More

Calix[n]arenes are macrocyclic cone-shaped compounds formed from phenolic units linked by methylene groups in the ortho position. Structural features make calix[n]arenes a versatile class of molecules that are of great interest, particularly in the pharmaceutical field. The cavity-like shape gives calix[n]arenes the ability to selectively encapsulate ions or neutral molecules, which can be used to generate carrier systems capa Read More

Non-covalent interactions like hydrogen bonding, hydrophobic interactions and salt bridges, have been our primary focus in designing and optimizing drugs. Recently, there is mounting evidence that non-covalent interactions involving aromatic rings are also potent forces for the recognition between small drug-like compounds and their targets. Understanding of these interactions and their physical origin is of signi Read More

The rapid increase of human infections by multidrug-resistant (MDR) Gram-negative pathogens poses a serious health threat and demands the identification of new strategies, molecular targets, and agents for the treatment of Gram-negative bacterial infections. The biosynthesis of lipid A, the membrane-anchoring portion of lipopolysaccharide (LPS), is one promising target for novel antibiotic design because lipid A is essent Read More

Ghrelin is a gut hormone that stimulates food intake. In physiological conditions, ghrelin plasma levels rise with fasting and decrease after meals. Obese individuals have low fasting ghrelin levels that rise after food restriction, which is pointed out as a reason for the difficulty in maintaining weight loss. Some bariatric surgery procedures prevent rise in ghrelin levels with weight loss and this has been hypothesised to contribut Read More