Developmental patterning pathways are essential for establishing the structural and functional architecture of the brain. These signaling pathways orchestrate early events such as neural induction, axis formation, regional identity, and neuronal differentiation. Although traditionally viewed as processes restricted to embryonic development, recent research reveals that these pathways remain active throughout life, where they continue to influence neuronal maintenance, synaptic stability, and neuroprotective responses. Dysregulation of these pathways during aging is increasingly recognized as a central contributor to the onset and progression of neurodegenerative disorders.

Neurodegenerative diseases such as Alzheimer disease, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis demonstrate significant links to these developmental pathways. Many genes implicated in these conditions regulate or respond to patterning signals, suggesting that neurodegeneration may reflect a re-emergence or maladaptive continuation of developmental programs. This connection highlights an important conceptual shift, viewing neurodegeneration not only as a result of toxic accumulation or neuronal loss but also as a consequence of lifelong alterations in pathways originally designed to guide brain development.

Understanding how developmental patterning pathways evolve with age may unlock new therapeutic approaches. Interventions that modulate signaling pathway, may restore neural stem cell function, enhance synaptic resilience, or dampen harmful inflammatory cascades. Emerging technologies such as single-cell transcriptomics, human brain organoids, and in vivo imaging provide unprecedented tools for mapping these pathway dynamics across the lifespan and in disease contexts. By revisiting the role of developmental patterning signals, researchers can explore innovative strategies that promote healthy brain aging and mitigate the progression of neurodegenerative conditions.

Potential areas of research but not limited to

• Mechanisms influencing neural plasticity and cognitive function during aging

• Factors affecting neural stem cell activity and regeneration in the aging brain

• Processes contributing to glial aging and age-associated inflammation

• Determinants of synaptic integrity and connectivity across the lifespan

• Interactions between developmental pathways and cellular stress in neurodegeneration

• Strategies to enhance or restore pathways that support healthy brain aging

• Role of developmental patterning mechanisms in shaping brain structure and function across aging

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Developmental Patterning Pathways Revisited: Roles in Brain Aging and Neurodegeneration