Writer contributions:
Design and idea of the manuscript: ACC, AGR, RO; literature search and manuscript preparation: ACC; manuscript modifying: ACC, RO. All authors reviewed the manuscript and authorized the ultimate manuscript.
Summary
The Collagen Superfamily, a Backward Look within the Nature of Kind XIX Collage
Looking standards included articles describing the next topics: “type XIX collagen, COL19A1, skeletal muscle, neurodegeneration, amyotrophic lateral sclerosis, structure, properties”. This evaluate consists of our expertise within the area of sort XIX collagen associated to amyotrophic lateral sclerosis (ALS), in addition to articles retrieved utilizing digital search of the PubMed database. Articles that have been printed as much as April 2019 have been included.
Molecular Characterization of Kind XIX Collagen
Contemplating that it comprises a thrombospondin like N-terminal area in NC6 and it’s not related to fibres, sort XIX collagen has additionally been described as a member of the multiplexin household, to which varieties XV and XVIII collagens belongs to (Myers et al., 1997; Sumiyoshi et al., 2001; Ricard et al., 2011). Albeit these similarities, sort XIX collagen as an entire is a singular collagen member that may play totally different roles relying on its localization. Moreover, the localization of sort XIX collagen within the basement membrane zone of various organs resembles the one noticed in different multiplexins.
A Extensive Vary of Expression Patterns and Features in Kind XIX Collage
Within the former stage it’s localized in particular areas corresponding to vasculature, neural and muscular basal membrane zone of skeletal muscle, spleen, pores and skin, kidney, colon, prostate and within the hippocampus within the mind (Oudart et al., 2013, 2017). Curiously, over the past decade some related research have analyzed the connection of sort XIX collagen with particular issues or ailments, corresponding to breast most cancers and melanoma and ALS. As a matter of truth, the susceptibility of sort XIX collagen to proteolysis or irregular ranges of synthesis may very well be concerned in several pathological states.
Proteolysis of Kind XIX Collagen Exerts an Anti-Angiogenic and Anti-Tumor Results
Subsequently, since ALS is characterised by a progressive muscle weak point in an analogous manner as in muscular dystrophy pathologies, our speculation is predicated on the truth that the activation of Col19a1 gene expression may additionally exert a compensatory response, most likely via the FAK pathway, to ameliorate muscle injury within the mice that will not have the ability to activate so effectively the muscle regeneration mechanisms. Specifically, below pathological circumstances corresponding to muscular dystrophies or spinal twine damage, FAK expression is considerably lowered within the skeletal muscle, whereas satellite tv for pc cells and myoblast differentiation are activated as a compensatory response for the muscle regeneration (Sakuma et al., 2004; Graham et al., 2015). Extra in depth, a big downregulation of myogenic regulatory components, corresponding to myogenin, was noticed on the presymptomatic levels of the illness in these mutant SOD1 cell cultures, suggesting that the compensatory response to ameliorate illness development is altered from early levels on this mouse mannequin (Manzano et al., 2013).
Irregular Ranges of Synthesis of Kind XIX Collagen Reveal Its Nature as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis
Within the circumstances by which the prognosis and prognosis of the illness is poor, as in ALS, the identification of potential biomarkers of illness in several tissues is a priceless instrument to watch the illness, even below remedy circumstances, and to amass a greater understanding of its development and ethiopathogenic origin. The detection and measurement of COL19A1 transcript and protein ranges in several tissues below pathological circumstances can make clear its position as a prognostic and/or diagnostic biomarker for human ailments. This examine offered proof that this collagen might be detected and measured in several human tissue extracts and organic fluids, corresponding to serum, amniotic fluid or twine blood.
Future Issues
In such totally different situations, sort XIX collagen exerts a regenerative and compensatory impact to gradual tumor development or to compensate the illness development below neurodegenerative circumstances particular to ALS. Exactly, this final organic position permits it to be thought of a dependable prognostic biomarker in a neurodegenerative illness of unknown origin as ALS, paving the best way to a greater stratification of ALS sufferers in medical trials and to extra environment friendly therapeutic methods to ameliorate the illness development. However, below physiopathological circumstances corresponding to tumors and neurodegenerative ailments like ALS, conformational adjustments in its molecular construction or altered transcript expression ranges present the organic impact of this collagen past its structural position in basement membranes.