Current Signal Transduction Therapy - Current Issue

Alzheimer's disease and diabetes are common disorders among the elderly population and have emerged as a major health concern. Both diseases pose considerable risks to one another. Diabetics have a significantly increased probability of getting Alzheimer's disease throughout their lifetime. These diseases are linked because, both share common risk factors such as impaired carbohydrate metabolism, insulin resistance, oxidative stress, inflammatory response, mitochondrial dysfunction, and amyloidosis. Insulin is a vital hormone responsible for bringing extremely high glucose levels back to normal and its receptors available in the hippocampus help in enhancing cognitive function. Insulin resistance consequently serves as a link between both diabetes and AD. Similarly, amylin is another hormone secreted by the pancreas along with insulin. During diabetes, amylin gets oligomerized and forms a neurotoxic complex with Aβ inside the brain, which causes AD to develop. Along with these, another main mechanism influencing AD development is Ca²⁺ dyshomeostasis. Insulin production from the pancreas is generally aided by Ca²⁺, but in excess, it can cause dysregulation of many signaling pathways such as CaMKK2, CAMP, CREB, MAPK, STIM\Orai, etc. which can ultimately result in the pathogenesis of AD in diabetic people. In this review, we discussed in detail the pathogenesis of AD associated with diabetes and the mechanisms initiating their progression.

Background: Erectile Dysfunction (ED) is a common sexual disorder among men aged 20 years and over. It is predominantly characterized by alterations in the key physiological pathways regulating erectile function, such as nitric oxide and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK). Beyond these pathways, multiple molecular signaling networks are involved in ED pathogenesis. Objective: This review aims to describe the major signal transduction pathways that impact erectile function and contribute to the introduction of the pathogenesis of ED. Methods: A literature review of ED was performed from 2000 to 2023 using PubMed, Scopus, and Embase. “ED” and “related signaling pathway”, “molecular mechanisms” terms were used. Results: Further basic and clinical studies are required to define the underlying molecular mechanisms of ED. The signaling pathways that were not affected by phosphodiesterase type 5 inhibitors (PDE5i) may be the reason for the reduced efficacy of this first-line treatment option in a variety of conditions. Conclusion: There is still a need for a deeper description of the molecular mechanisms in terms of fibrosis, angiogenesis, apoptosis, inflammation, oxidative stress, autophagy, and hypoxia to identify new possible targets underlying the pathogenesis of ED. This comprehensive review expounds on the principal signaling pathways, offering valuable insights that may catalyze the development of innovative and enhanced therapies for managing ED.

Long non-coding RNAs (lncRNAs), characterized by their length exceeding 200 nucleotides and lack of protein-coding capacity, are intricately associated with a wide array of cellular processes, encompassing cell invasion, differentiation, proliferation, migration, apoptosis, and regeneration. Perturbations in lncRNA expression have been observed in numerous diseases and have emerged as pivotal players in the pathogenesis of diverse tumor types. Glioblastoma, a highly malignant primary tumor of the central nervous system (CNS), remains a formidable challenge even with the advent of novel therapeutic interventions, as primary glioblastomas invariably exhibit therapy resistance and aggressive behavior. Glioblastomas can arise from progenitor cells or neuroglial stem cells, revealing profound cellular heterogeneity, notably in the form of glioblastoma stem cells (GSCs) possessing stem-like properties. Glioblastomas comprise neural precursors that harbor essential characteristics of neural stem cells (NSCs). Several signaling pathways have been implicated in the regulation of self-renewal in both cancer cells and stem cells. In addition to their involvement in therapy resistance and survival of glioblastoma, lncRNAs are implicated in the modulation of GSC behaviors through diverse pathways and the intricate regulation of various genes and proteins. This review aims to comprehensively discuss the interplay between lncRNAs, their associated pathways, and GSCs, shedding light on their potential implications in glioblastoma.