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Gelsolin’s multifunctional roles in health and diseases.

Gelsolin, is an ubiquitous, multifunctional regulator of cell structure and metabolism. Gelsolin has manifold impacts on cancer, apoptosis, infection and inflammation, cardiac injury, pulmonary diseases, and aging. Recently, gelsolin has been implicated in cell survival signalling pathways and Intestinal inflammation, proliferation, apoptosis (PMID: 22886630), cellular invasiveness in NK/T-cell lymphoma cells (PMID: 29175858),  ovarian cancer (PMID: 28599499),  prostate cancer (PMID: 29100377), and other disorders. An improved understanding of the functions and regulatory mechanisms of gelsolin may lead to new considerations of this protein as a potential biomarker and/or therapeutic target

Gelsolin: a molecular gymnast.

Gelsolin superfamily members are Ca(2+) -dependent, multidomain regulators of the actin cytoskeleton. Calcium binding activates gelsolin by inducing molecular gymnastics (large-scale conformational changes) that expose actin interaction surfaces by releasing a series of latches. Molecular flexibility in gelsolin-like proteins permits cells to exploit the force generated from actin polymerization to drive processes such as cell movement in health and disease (PMID: 23749648).

 Hereditary Gelsolin Amyloidosis (HGA).

Hereditary gelsolin amyloidosis (HGA) is an autosomal dominantly inherited amyloid disorder. 

Researchers believe that HGA, originally reported in Finland and now increasingly in other countries in Europe, North and South America, and Asia, may still be underdiagnosed worldwide. The first Italian family affected by HGA was reported very recently, in March 2017; the first Korean case was reported in 2016 ( PMID: 26915616). The disease is characterised by adult-onset slowly progressive cranial neuropathy (condition affecting cranial nerves), lattice corneal dystrophy, and cutis laxa.  It is the first and so-far only known disorder caused by a gelsolin gene defect, specifically, a G654A or G654T mutation. This point mutations in the gelsolin (GSN) gene (G654A being the most common one) results in disturbed calcium binding by the second gelsolin domain (G2). As a result, the folding of G2 is hampered, rendering the mutant plasma gelsolin susceptible to a proteolytic cascade. Consecutive cleavage by proteases generates 8 and 5 kDa amyloidogenic peptides that cause neurological, ophthalmological and dermatological disorders.  To this day, no specific treatment is available to counter the pathogenesis. It has been recently proposed PMID: 25601851  that nanobodies can be used to shield substrates from aberrant proteolysis and this approach might establish a novel therapeutic strategy in amyloid diseases.  

                   Now you can buy this unique human recombinant gelsolin product, from BioAspect.

                                                              ORDER HUMAN RECOMBINAT GELSOLIN

                                                              Any questions? E-mail: inquiries@bioaspect.com