Proteases are expressed by normal cells in tissue remodeling events and also during pathological events such as tumor invasion and metastasis. Some of the proteases including serine proteinases and MMPs (Metalloproteinases) have been implicated in remodeling of the ECM (Extracellular Matrix) in lung injury and lung neoplasia. These enzymes influence inflammatory cell traffic or cancer cell invasiveness via the breakdown of basement membranes and ECM. Plasmin, a serine protease, is involved in the dissolution of ECM and basement membrane during tissue degradation. This protease is generated via the action of plasminogen activators such as Urokinase (UPA, Urokinase-type Plasminogen Activator) or Urokinase (tissue Plasminogen Activator) and can influence tissue remodeling[..]

Neurotrophins are an important class of signaling molecules in the brain responsible for axon targeting, neuron growth, maturation of synapses during development, and synaptic plasticity. This family of molecules includes NGF (Nerve Growth Factor), BDNF (Brain Derived Neurotrophic Factor), NT3 (Neurotrophin-3) and NT4 (Neurotrophin-4) [Ref.1].Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that support differentiation, maturation, and survival of neurons in the nervous system and shows a neuroprotective effect under adverse conditions, such as glutamatergic stimulation, cerebral ischemia, hypoglycemia, and neurotoxicity. BDNF stimulates and controls growth of new neurons from neural stem cells (neurogenesis) and BDNF protein and mRNA have[..]

Sodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal nephron and colon is the major factor determining total body Na+ levels, and thus, long term blood pressure. Aldosterone, a steroid hormone that is primarily produced in the outer layer of the adrenal cortex, maintains total organism sodium balance in all higher vertebrates. Principally, in humans, aldosterone is involved in the regulation of electrolyte and water balance through its effects on ion transport in epithelial cells. Electrically tight epithelial monolayers, such as the renal distal tubule and collecting duct system, distal colon, and those in salivary glands, are considered classic aldosterone target tissues. Aldosterone plays a major role in Na+, K+, and H+[..]

Neurotrophic factors are a broad set of peptide growth factors that tightly regulate many critical aspects of the ontogeny of neurons, such as the number of neurons in a given population, neurite branching and synaptogenesis, adult synaptic plasticity and maturation of electrophysiological properties. Neurotrophic factors include Neurotrophins, Neurokines and GDNF (Glial-cell-line-derived Neurotrophic Factor) family ligands (GFLs). GDNF family, consisting of GDNF, NRTN (Neurturin), ARTN (Artemin) and PSPN (Persephin) are distant members of the TGF-Beta (Transforming Growth Factor-Beta) superfamily that maintain several neuronal populations in the CNS (Central Nervous Systems), including midbrain dopamine neurons. In addition, GDNF, NRTN and ARTN support the survival[..]

CRH (Corticotropin-Releasing Hormone) and related peptides play a major role in coordinating the behavioral, endocrine, cardiovascular, autonomic and immune mechanisms that allow mammals to adapt under both basal and stressful conditions. Their actions are mediated through activation of two types of GPCRs (G-Protein-Coupled Receptors): CRHR1 (CRH Receptor-1) and CRHR2 (CRH Receptor-2) encoded by separate genes. CRH and CRH-related peptides and their receptors are widely distributed in the central nervous system, and in a variety of peripheral tissues, including the immune, cardiovascular and reproductive systems, adrenals, lungs, liver, stomach, pancreas, small intestine, skin tissues, and also in some types of human tumors. The ubiquitous distribution of CRH-related[..]

AD (Alzheimer's Disease) is a neurodegenerative disorder leading to amnesia, cognitive impairment, and senile dementia. Two types of lesions characterize the disease: SPs (Amyloid or Senile Plaques) resulting from the extracellular aggregation of ABeta (Amyloid Beta) peptide, which is derived from a ubiquitous type I transmembrane protein named APP (Amyloid Precursor Protein), and NFTs (Neuro-Fibrillary Tangles) composed of intraneuronal bundles of PHF (Paired Helical Filaments). PHF result from the aggregation of pathologic Tau proteins, named PHF-Tau1. Both lesions extend progressively to neocortical brain areas during the course of Alzheimer Disease. The link between Amyloid deposits and NFTs is not yet clear. The vast majority of cases of Alzheimer Disease are[..]

WNV (West Nile Virus) is a single-stranded positive-polarity enveloped virus with icosahedral symmetry virus and the etiologic agent of West Nile encephalitis. It is a member of the Japanese encephalitis virus antigenic group within the family Flaviviridae, which can cause fatal encephalitis associated with damage to the CNS (Central Nervous System) in humans and animals. Wild birds are the natural reservoir (amplifying) hosts, and WNV transmission cycle primarily involving Culex sp mosquitoes. Initially isolated in 1937, it is now recognized as one of the most widely distributed flaviviruses, endemic in Africa, Europe, the Middle East, and parts of Asia. Since 1999, the virus has been recognized in North America by causing an epizootic among birds and horses[..]

The 14-3-3 family of proteins consists of molecular adaptors that recognize phosphorylated proteins (e.g. kinases, transcription factors and receptors). They are able to coordinate almost limitless combinations of protein complexes, which accounts for their functional diversity (Ref.1). This plethora of interacting proteins allows 14-3-3 to play important roles in a wide range of vital regulatory processes, such as neuronal development, mitogenic signal transduction, apoptotic cell death, cell cycle control, cell growth control, and viral and bacterial pathogenesis. More than 50 signaling proteins have been reported as 14-3-3 ligands (Ref.1). Seven mammalian isoforms of 14-3-3 proteins (α/β, ɛ, η, γ, τ/θ, δ/ζ, σ) have[..]

14-3-3 is a phosphoserine/phosphothreonine-binding protein that is being implicated in a wide range of cellular phenomena. 14-3-3 family members are found in all eukaryotes – from plants to mammals – and more than 100 binding partners have been identified to date. They regulate their activities by a number of different mechanisms, which include inter- and intracompartmental sequestration, activation/inactivation of enzymatic activity and promotion/inhibition of protein interactions. The targets of 14-3-3 are found in all sub cellular compartments and their functional diversity is overwhelming – they include transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors (Ref.1 & 2).[..]

CTLA4 (CD152) is a member of a class of cell surface molecules capable of terminating early events in the receptor-mediated signaling cascade. It is a 41–43 kDa,type 1 transmembrane glycoprotein of the immunoglobin superfamily having 223 amino acids in length. The extracellular architecture of CTLA4 is characterized by a single IgV-like domain containing the B7- 1 (CD80)/B7-2 (CD86) ligand-binding site. Expression of CTLA4 is dependent both on TCR stimulation by the antigens and CD28-B7 engagement. The costimulatory CTLA4 pathway, attenuates or downregulates T cell activation and CTLA4 is designed to remove body cells displaying "foreign" epitope, such as virus-infected cells, cells containing intracellular bacteria, and cancer cells with mutant surface proteins. The[..]

Nontypeable Haemophilus influenzae (NTHi) organisms are small Gram-negative bacteria that colonize the upper respiratory tract of humans beginning at a very early age. NTHi is also a leading cause of otitis media (OM), sinusitis, and community-acquired pneumonia, often following viral respiratory infection. A rising proportion of otitis media caused by NTHi has been attributed to widespread use of the pneumococcal conjugate vaccine, which was introduced in the year 2000 and has reduced the incidence of respiratory infections caused by Streptococcus pneumonia Among adults, particularly among patients with chronic obstructive pulmonary disease (COPD), NTHi infections are a major cause of illness, especially during the acute exacerbations that often characterize[..]

The internal osmolarity of a growing yeast cell is maintained higher than the external osmolarity. The resulting osmotic gradient across the plasma membrane brings in water for cell expansion and creates turgor. Yeast cells are quite resistant to various types of stress including hypertonic stress. This adaptability can be traced to stress-activated signaling pathways that sense the stress condition and activate expression of proteins that resist the toxic effects of the stress and promote survival and eventual cell growth under the new conditions. In Saccharomyces cerevisiae, changes in the osmolarity of the medium have been reported to affect different signaling pathways. The best-characterized signaling system by far involves the MAPK (Mitogen-Activated Protein[..]