Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an uncommon disorder associated with genes characterized by the gradual weakening and deterioration of muscles, often leading to substantial disability and premature mortality. Over the past decade, remarkable strides have been made in the field of SMA therapeutics, revolutionizing the landscape of patient care. One pivotal advancement is the development of gene-targeted therapies, such as nusinersen, onasemnogene abeparvovec and risdiplam which have demonstrated unprecedented efficacy in slowing disease progression. These therapies aim to address the root cause of SMA by targeting the survival motor neuron (SMN) gene, effectively restoring deficient SMN protein levels. The advent of these innovative approaches has transformed the prognosis for many SMA patients, offering a glimmer of hope where there was once limited therapeutic recourse. Furthermore, the emergence of small molecule compounds and RNA-targeting strategies has expanded the therapeutic arsenal against SMA. These novel interventions exhibit diverse mechanisms of action, including SMN protein stabilization and modulation of RNA splicing, showcasing the multifaceted nature of SMA treatment research. Collective efforts of pharmaceutical industries, research centers, and patient advocacy groups have played an important role in expediting the translation of scientific discoveries into visible clinical benefits. This review not only highlights the remarkable progress achieved in SMA therapeutics but also generates the ray of hope for the ongoing efforts required to enhance accessibility, optimize treatment strategies, rehabilitation (care and therapies) and ultimately pave the way for an improved quality of life for individuals affected by SMA.

Cross Talk Between Renal Transporters and Polycystin-1 as a Potential Molecular Target Involved in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: The mutational changes in Polycystin-1(PC-1) encoded by PKD1 gene is the main cause of Autosomal Dominant Polycystic kidney disease (ADPKD). The pathological changes in renal epithelial cells and multiple cyst formation occur due to activation of cascade of signalling pathways and membrane renal transporters (RTs). Our study have focused on the identification, of different RTs, their interactions with Polycystin-1 and other selected target proteins to find out their role in pathogenesis. METHODS: In this study, various RTs protein sequences were identified and retrieved from NCBI's GenBank and UniProt. RTs were categorized according to different nephronal segmenta as per their functional information retrieved from UniProt and Transpoter databases. Further, sequences were subjected for interaction network analysis in String database and Cytoscape 3.7.2. Different interactions including experimentally validated were identified and can be further validated through in vivo methods. RESULTS: The cross talk between different RT, Polycystin-1 and other sequences were analysed. The various pathways of the interaction with PC-1 were categorised. The total number of 119 nodes and 769 edges interactions were generated. The results were visualized and cross verified with other databases in cytoscape. CONCLUSION: The cross signalling of PKD1 with SCNN1A, SCNN1G, SLC12A1, AVPR2 shows their importance in the cyst formation and in pathogenesis of ADPKD.

Molecular cloning, characterization, heterologous expression and in-silico analysis of disordered boiling soluble stress-responsive wBsSRP protein from drought tolerant wheat cv.PBW 175.

The structural and physico-chemical properties that account for the multi-functionality of dehydrins remain largely unknown. In this study, we identified, sequenced and cloned a stress regulated cDNA encoding a dehydrin-like boiling stable protein (designated as wBsSRP; wheat boiling stable stress responsive protein) from drought stressed seedlings of drought tolerant cultivar of wheat (PBW 175). qRT-PCR analysis documented high transcripts levels of wBsSRP during drought and cold conditions in the tolerant cv. PBW 175 as a part of adaptive response to stress while the levels were significantly lower in the sensitive cv. PBW 343. We also describe in-silico characterization and molecular modeling of wBsSRP through homology search, motif analysis, secondary structure prediction, active site prediction and 3D structure analysis. The physico-chemical properties and theoretical data of wBsSRP depicts that it is a canonical group 2 LEA protein. The recombinant wBsSRP protein when expressed in E. coli detected a specific differential band (∼11 kDa) on SDS- PAGE after IPTG induction. The functional analysis of wBsSRP in E. coli revealed that wBsSRP is essential for the survival of E. coli as well as for maintaining bacterial growth under various stress conditions. In vitro peroxidase protection assay during heat stress (50 and 100 °C) showed that in the presence of wBsSRP, peroxidase activity was significantly retained and/or increased. Based upon the findings, it is suggested that wBsSRP accentuated the effects of stress by acting as a protectant and by the stabilization of membranes, thereby contributing to the improved stress tolerance of the recombinant E. coli under various abiotic stress conditions. We suggest that these findings might provide the rationale for the mechanism of how these proteins obviate the adverse effects of dehydration stress.

In silico analysis, annotation and characterisation of putative ESTs from Sorghum bicolor associated with heat stress.

Owing to their sessile nature, plants experience a variety of environmental stresses, but tolerance to these adverse conditions is a very complex phenomenon. Among all stresses, heat stress is the most important constraint that affects plant yield in rain-fed areas. To shed some light on candidate genes involved in heat stress, sequences potentially associated with heat shock resistance were retrieved and identified by in silico analysis using the public sequence database of various plants. A total of 30,000 EST sequences were mined and 24 putative ESTs associated with heat stress were picked up for further studies. In silico analysis revealed that all ESTs were linked with the HSP family. Gene Ontology (GO) analysis revealed that the deduced protein sequences of the heat-linked 24 ESTs were involved in various biological pathways regulating heat stress response. Hydropathy analysis revealed that all protein sequences were hydrophilic in nature. Based on the phylogenetic analysis, all HSP-related protein sequences were divided into seven groups. Analysis of cis-elements provides molecular evidence for the possible involvement of hydrophilic ESTs in the process of abiotic stress tolerance in sorghum. Based on these results, it was suggested that putative ESTs may play an important role in heat stress tolerance.

In silico analysis of putative miRNAs and their target genes in sorghum (Sorghum bicolor).

MicroRNAs (miRNAs) are small endogenous genes regulators which regulate different processes underlying plant adaptation to abiotic stresses. To gain a deep understanding of role of miRNAs in plants, in the present study, we computationally analyzed different sorghum miRNAs in the drought-induced gene sequences. Homologous miRNA were identified using different plant miRNA databases. Using previously established genes databases, various targets of sorghum miRNAs were predicted viz: transcription factors, chaperonins, metabolic enzymes and other gene targets necessary for proper plant development. Analysis of cis-elements provides molecular evidence for the possible involvement of miRNAs in the process of abiotic stress tolerance in sorghum. Based on these results, it was suggested that miRNAs may play an important role in water stress tolerance.