Neural stem cell secretome: Mechanisms and therapeutic potential in regulating neuroplasticity and aging-related neurodegeneration

Aging profoundly impacts the nervous system, leading to diminished neuroplasticity and increased susceptibility to neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD). Neural stem cells (NSCs) and their secreted factors, including growth factors, immunomodulatory cytokines, and extracellular vesicles (EVs), play critical roles in regulating neuroplasticity and counteracting age-related neural decline. This review synthesizes recent findings on how NSC secretions orchestrate synaptic plasticity, hippocampal neurogenesis, and glial crosstalk, which collectively support learning, memory, and neural repair. Aging disrupts this balance by reducing trophic factor secretion and promoting a pro-inflammatory secretome, exacerbating synaptic loss and cognitive impairment in AD and PD. Rejuvenation strategies, including neurotrophic factor delivery and lifestyle interventions like caloric restriction and exercise, show promise in restoring neuroplasticity and mitigating neurodegeneration. By integrating mechanistic insights for NSCs secretome-mediated regulation, this review underscores the therapeutic potential of targeting the NSCs secretome to enhance neural resilience and combat age-related cognitive decline, offering a new perspective for developing preventive and therapeutic strategies in aging and neurodegenerative disorders.