Recent Patents on Endocrine Metabolic & Immune Drug Discovery

ISSN: 1872-2148


OPEN ACCESS ARTICLES


Contents


Fetuin-A: A Multifunctional Protein, 2011, 5, 124-146
Katsuhito Mori, Masanori Emoto and Masaaki Inaba
[Abstract] [Full Text Article]


Chitin and β-Glucan Polysaccharides as Immunomodulators of Airway Inflammation and Atopic Disease, 2010, 4, 175-189
Adriana Catalli and Marianna Kulka
[Abstract] [Full Text Article]


Hepatic Nuclear Factor-4, a Key Transcription Factor at the Crossroads Between Architecture and Function of Epithelia, 2007, 1, 166-175
Agnès Ribeiro, Amena Archer, Johanne Le Beyec, Anne-Laure Cattin, Susan Saint-Just, Martine Pinçon-Raymond, Jean Chambaz, Michel Lacasa and Philippe Cardot
[Abstract] [Full Text Article]



Abstracts



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Fetuin-A: A Multifunctional Protein
Katsuhito Mori, Masanori Emoto and Masaaki Inaba

[Full Text Article]

Sixty-six years have elapsed since the discovery of fetuin in 1944, but its importance in mammalian physiology has only recently been appreciated. Fetuin, first isolated from fetal bovine serum and now most commonly known as either fetuin-A, alpha-2-HS-glycoprotein (recommended name by UniprotKB and PIR), or α2-Heremans-Schmid glycoprotein, functions as an important component of diverse normal and pathological processes, including vascular calcification and bone metabolism regulation, insulin resistance, protease activity control, keratinocytes migration, and breast tumor cell proliferative signaling. Fetuin-A has also been identified as a biomarker for neurodegenerative disease. Here, we summarize recent publications focusing on the structural and functional properties of fetuin-A. The emerging importance of fetuin-A for both diagnosis and therapeutics has come to the attention of the pharmaceutical industry. Therefore, we will discuss the status of patents based on fetuin-A.


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Chitin and β-Glucan Polysaccharides as Immunomodulators of Airway Inflammation and Atopic Disease
Adriana Catalli and Marianna Kulka

[Full Text Article]

Polysaccharides are receiving increased attention due to their clinical applications in tissue engineering, vaccine development, nutritional supplementation and antimicrobial biopolymer engineering. The most abundant polysaccharides include fungal cell wall components chitin and β-1,3-glucans. Recent evidence has shown that these polysaccharides modulate airway inflammation, making them the basis of several drug discovery platforms. Small to intermediate chitin fragments (< 70 μm) are protective in allergic inflammatory models, skewing T cell immunity towards Th1 responses, and reducing the production of Th2 cytokines. As such, chitin prevents the development of the quintessential features of asthmatic disease including chronic airway inflammation, airway hyperresponsiveness and pathological remodeling changes in mouse models of allergy. In contrast, the in vivo effects of β-glucans in animal models of airway inflammation are often contradictory, and the number of human studies is limited. β-1,3-glucans are both pro- and anti-inflammatory, preventing and enhancing allergic inflammation depending on the preparation, purity and species origin of the β-glucans. This review summarizes recent studies of chitin and β-glucans in models of atopy and airway inflammation and examines the possible reasons for the apparently contradictory observations. Recent relevant patents are also highlighted.


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Hepatic Nuclear Factor-4, a Key Transcription Factor at the Crossroads Between Architecture and Function of Epithelia
Agnès Ribeiro, Amena Archer, Johanne Le Beyec, Anne-Laure Cattin, Susan Saint-Just, Martine Pinçon-Raymond, Jean Chambaz, Michel Lacasa and Philippe Cardot

[Full Text Article]

Hepatic nuclear factor-4 (HNF-4) is a transcription factor and a member of the large family of nuclear receptors. It was first cloned from liver but is expressed also in kidney, pancreas and intestine. Three genes encoding three isoforms have been identified, HNF-4α and γ, in mammals, drosophila and xenopus and HNF-4β, exclusively in xenopus. HNF-4α is the best studied isoform, especially in liver. Such studies put HNF-4α at the crossroads between architecture and function of epithelia, as it induces expression of cell/cell junction proteins while it also controls glucido-lipidic metabolism and drug metabolizing enzyme genes. Furthermore, mutations in the HNF-4α gene lead to a metabolic disease in humans, Maturity Onset Diabetes of the Young-1 (MODY-1). The existence of a “true ligand” is not clearly established but a “structural” fatty acid is present in the ligand binding pocket of HNF-4α and γ. Consequently, activity of HNF-4 can be modulated by the interaction with co-regulators or by post-translational modifications. Then, HNF-4 is a potential direct or indirect target for pharmacologic drugs, with a special interest for the intestinal epithelium which is the primary site of metabolic control, due to its roles in nutrient absorption and in sensing energy. The patents related to the HNF-4α gene are also discussed in this article.