Mitogen-Activated Protein Kinase Pathway in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis is a fatal motor neuron degenerative disease. Multiple genetic and non-genetic risk factors are associated with disease pathogenesis, and several cellular processes, including protein homeostasis, RNA metabolism, vesicle transport, etc., are severely impaired in ALS conditions. Despite the heterogeneity of the disease manifestation and progression, ALS patients show protein aggregates in the motor cortex and spinal cord tissue, which is believed to be at least partially caused by aberrant phase separation and the formation of persistent stress granules. Consistent with this notion, many studies have implicated cellular stress, such as ER stress, DNA damage, oxidative stress, and growth factor depletion, in ALS conditions. The mitogen-activated protein kinase (MAPK) pathway is a fundamental mitogen/stress-activated signal transduction pathway that regulates cell proliferation, differentiation, survival, and death. Here we summarize the fundamental role of MAPK in physiology and ALS pathogenesis. We also discuss pharmacological inhibitors targeting this pathway tested in pre-clinical models, suggesting their role as potential drug candidates.

Correction to: Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD.

An amendment to this paper has been published and can be accessed via the original article.

A novel exopolysaccharide from marine bacterium Pantoea sp. YU16-S3 accelerates cutaneous wound healing through Wnt/ß-catenin pathway.

Natural polysaccharides with versatile properties are the potential candidates for wound healing applications. In this study, an exopolysaccharide, EPS-S3, isolated from a marine bacteria Pantoea sp. YU16-S3 was evaluated for its wound-healing abilities by studying the key molecular mechanisms in vitro and in vivo. Basic characterisation showed EPS-S3 as a heteropolysaccharide with glucose, galactose, N-acetyl galactosamine and glucosamine. The molecular weight of EPS-S3 was estimated to be 1.75 × 105 Da. It showed thermal stability up to 200 °C and shear-thickening non-Newtonian behaviour. It was biocompatible with dermal fibroblasts and keratinocytes and showed cell adhesion and cell proliferation properties. EPS-S3 facilitated cell migration in fibroblasts, induced rapid transition of cell cycle phases and also activated macrophages. In vivo experiments in rats showed the re-epithelialization of injured tissue with increased expression of HB-EGF, FGF, E-cadherin and ß-catenin in EPS-S3 treatment. The results indicate that EPS-S3 modulates healing process through Wnt/ß-catenin pathway due to its unique characteristics. In conclusion, EPS-S3 biosynthesized by the marine bacterium is a potential biomolecule for cutaneous wound healing applications.

A bioactive exopolysaccharide from marine bacteria Alteromonas sp. PRIM-28 and its role in cell proliferation and wound healing in vitro.

Marine bacteria secrete exopolysaccharides (EPS) with unique structural and functional properties and serve as a source of newer bioactive biopolymers. This study reports an EPS produced by a marine bacterium identified as Alteromonas sp. PRIM-28 for its bioactivities. The EPS was characterised using standard methods and tested for its bioactivities using in vitro models. EPS-A28 is an anionic heteropolysaccharide with a molecular weight of 780 kDa and exists as triple helical structure in aqueous solution. Monosaccharide composition is mannuronic acid, glucose and N-acetyl glucosamine repeating units in the ratio 1:3.67:0.93. The FT-IR spectra showed the presence of sulphate, phosphate and uronic acid residues. The thermal analysis showed partial degradation of the EPS-A28 at 190 °C and 40% of residues were stable up to 800 °C. It showed biocompatibility and induced proliferation and migration of dermal fibroblasts (HDF) and keratinocytes. EPS-A28 could increase the S-phase of cell cycle. The proliferative property of the EPS-A28 was established by the increased expression of fibroblast proliferation marker (Ki-67) also its capability of binding to cell surface. It also induced nitric oxide and arginase synthesis in macrophages. These findings suggest that EPS-A28 can be potentially used as a multifunctional bioactive polymer in wound care.

Biopolymers: Applications in wound healing and skin tissue engineering.

Wound is a growing healthcare challenge affecting several million worldwide. Lifestyle disorders such as diabetes increases the risk of wound complications. Effective management of wound is often difficult due to the complexity in the healing process. Addition to the conventional wound care practices, the bioactive polymers are gaining increased importance in wound care. Biopolymers are naturally occurring biomolecules synthesized by microbes, plants and animals with highest degree of biocompatibility. The bioactive properties such as antimicrobial, immune-modulatory, cell proliferative and angiogenic of the polymers create a microenvironment favorable for the healing process. The versatile properties of the biopolymers such as cellulose, alginate, hyaluronic acid, collagen, chitosan etc have been exploited in the current wound care market. With the technological advances in material science, regenerative medicine, nanotechnology, and bioengineering; the functional and structural characteristics of biopolymers can be improved to suit the current wound care demands such as tissue repair, restoration of lost tissue integrity and scarless healing. In this review we highlight on the sources, mechanism of action and bioengineering approaches adapted for commercial exploitation.