Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability and neuronal loss. This review explores the contrasting role of OS in cancer stem cells (CSCs) and NDDs. Elevated levels of reactive oxygen species (ROS) contribute to genomic instability and promote tumor initiation and progression in CSCs, while in NDDs such as Alzheimer’s and Parkinson’s disease, OS accelerates neuronal death and impairs cellular repair mechanisms. Both scenarios involve disruption of the delicate balance between pro-oxidant and antioxidant systems, which leads to chronic oxidative stress. Notably, CSCs and neurons display alterations in redox-sensitive signaling pathways, including Nrf2 and NF-κB, which influence cell survival, proliferation, and differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function in CSCs supports adaptability and survival, whereas impairments in neurons heighten vulnerability. Understanding these common mechanisms of OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, and potentially mitigating or preventing both cancer and NDDs.

The highly conserved Notch pathway, a pillar of juxtacrine signaling, orchestrates intricate intercellular communication, governing diverse developmental and homeostatic processes through a tightly regulated cascade of proteolytic cleavages. This pathway, culminating in the migration of the Notch intracellular domain (NICD) to the nucleus and the subsequent activation of downstream target genes, exerts a profound influence on a plethora of molecular processes, including cell cycle progression, lineage specification, cell–cell adhesion, and fate determination. Accumulating evidence underscores the pivotal role of Notch dysregulation, encompassing both gain and loss-of-function mutations, in the pathogenesis of numerous human diseases. This review delves deep into the multifaceted roles of Notch signaling in cellular dynamics, encompassing proliferation, differentiation, polarity maintenance, epithelial–mesenchymal transition (EMT), tissue regeneration/remodeling, and its intricate interplay with other signaling pathways. We then focus on the emerging landscape of Notch aberrations in gynecological pathologies predisposing individuals to infertility. By highlighting the exquisite conservation of Notch signaling in Drosophila and its power as a model organism, we pave the way for further dissection of disease mechanisms and potential therapeutic interventions through targeted modulation of this master regulatory pathway.

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited effective therapies. In this study, a series of 2-(arylamino)thiazol-4(5H)-one derivatives was synthesized using an efficient microwave-assisted protocol, and evaluated for neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress (OS) in SH-SY5Y neuronal cells and an Aβ42-expressing Drosophila melanogaster model of AD. Among the synthesized compounds, 3n, 3i, and 3b exhibited low cytotoxicity and significant neuroprotection, as evidenced by increased cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. Notably, compound 3n demonstrated the highest activity and effectively ameliorated Aβ42-induced behavioral deficits in vivo. Molecular docking studies predicted favorable binding affinity within the acetylcholinesterase (AChE) active site, with the thiazol scaffold and aryl substituents stabilizing ligand binding through π–π stacking and hydrophobic interactions; compound 3n also formed additional hydrogen bonds enhancing its affinity. Consistent with the docking predictions, in vitro AChE inhibition studies demonstrated that compounds 3n, 3i, and 3b inhibited AChE in a concentration-dependent manner. Network pharmacology predicted seven potential core targets implicated in AD pathogenesis and related pathways, including OS, neuroinflammation, and synaptic dysfunction. Furthermore, in silico pharmacokinetic analysis indicated compliance with Lipinski’s and Veber’s rules, supporting favorable drug-like properties. While further experimental validation is essential, these findings highlight 2-(arylamino)thiazol-4(5H)-one derivatives, particularly compound 3n, as promising multifunctional candidates for further preclinical development against AD.