Molecular Dysregulation of Neural Stem Cell Fate Decisions in Neurodegenerative and Neoplastic Brain Disorders

Neural stem cells (NSCs) sustain cellular plasticity in the developing and adult brain through tightly coordinated molecular programs that regulate quiescence, activation, and lineage commitment. Disruption of these programs is increasingly recognized as a central feature of neurological disorders, including neurodegenerative diseases and brain tumors, yet the molecular logic by which disease states reshape NSC fate decisions remains incompletely understood. Neurodegenerative conditions, including Alzheimer’s and Parkinson’s disease, as well as neoplastic disorders such as glioblastoma, represent key disease contexts in which aberrant NSC regulation has been implicated, making them important frameworks for understanding how molecular programs break down in the diseased brain.This Research Topic provides a platform for studies investigating the molecular mechanisms governing NSC behavior in both physiological and pathological contexts. Contributions will focus on transcriptional and epigenetic regulation, gene regulatory network dynamics, metabolic control, and niche-derived signaling pathways that collectively shape NSC identity and plasticity. Particular emphasis will be placed on how disease-associated stressors, such as inflammation, proteostatic imbalance, metabolic dysfunction, and oncogenic signaling, alter molecular decision-making in NSCs, leading to impaired neurogenesis, maladaptive differentiation, or pathological self-renewal. By integrating molecular neuroscience across developmental, degenerative, and oncogenic paradigms, this Research Topic seeks to advance a unified understanding of how NSC fate is regulated and dysregulated in the brain, and to identify molecular nodes that may inform future therapeutic strategies.The Topic welcomes original research, reviews, and perspective articles employing molecular, cellular, and systems-level approaches, including single-cell and spatial profiling strategies, to resolve heterogeneous NSC states and transitional trajectories in health and disease. Topics of interest include, but are not limited to:- Transcriptional and epigenetic regulation of NSC quiescence, activation, and differentiation- Gene regulatory network dynamics governing NSC identity and lineage commitment- Metabolic control of NSC fate and plasticity- Niche-derived and paracrine signaling in NSC maintenance and injury response- Inflammatory and proteostatic stress as drivers of impaired neurogenesis- Oncogenic reprogramming of NSC fate in glioblastoma and related brain tumors- NSC dysfunction in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases- Single-cell and spatial transcriptomic approaches to resolving NSC heterogeneity and transitional cell states Topic editors: Shubham Garg, Vishal K Chavda, Carol Schuurmans Source: https://www.frontiersin.org/research-topics/82601/molecular-dysregulation-of-neural-stem-cell-fate-decisions-in-neurodegenerative-and-neoplastic-brain-disorders