Neuronal guidance signaling in neurodegenerative diseases: key regulators that function at neuron-glia and neuroimmune interfaces

• DOI: 10.4103/nrr.nrr-d-24-01330
• Publication Date: 2025-02-25T07:01:55Z
• Authors: Junichi Yuasa-Kawada; Mariko Kinoshita-...; Masaki Hiramoto; Satoru Yamagishi; Takayasu Mishima; Shin’ichiro Yasunaga; Yoshio Tsuboi; Nobutaka Hattori; Jane Y. Wu

Abstract The nervous system processes a vast amount of information, performing computations that underlie perception, cognition, and behavior. During development, neuronal guidance genes, which encode extracellular cues, their receptors, downstream signal transducers, organize neural wiring to generate the complex architecture system. It is now evident many these neuroguidance cues receptors are active during development also expressed in adult This suggests pathways critical not only for but ongoing function maintenance mature Supporting this view, continue regulate synaptic connectivity, plasticity, remodeling, overall brain homeostasis throughout adulthood. Genetic transcriptomic analyses have further revealed genes be associated with wide range neurodegenerative neuropsychiatric disorders. Although precise mechanisms by aberrant signaling drives pathogenesis diseases remain clarified, emerging evidence points several common themes, including dysfunction neurons, microglia, astrocytes, endothelial cells, along dysregulation neuron-microglia-astrocyte, neuroimmune, neurovascular interactions. In review, we explore recent advances understanding molecular cellular contributes disease through altered cell–cell For instance, studies unveiled two distinct semaphorin-plexin affect microglial activation neuroinflammation. We discuss challenges ahead, therapeutic potentials targeting treating diseases. Particular focus placed on how control neuron-glia neuroimmune interactions modulate under physiological pathological conditions. Specifically, examine crosstalk between TREM2, master regulator function, context pathogenic protein aggregates. well-established age major risk factor neurodegeneration. Future research should address aging interact influence an individual’s susceptibility various late-onset neurological progression could therapeutically blocked pathways.