Current Knowledge in Planarian Glia and Its Future Implications in Modeling Neurodegenerative Diseases

Neurodegenerative diseases are characterized by progressive loss of neurons and remain largely incurable. Numerous mammalian models have been developed to study the mechanisms underlying their physiopathology; however, their high cost, complexity and time requirements highlight the need for alternative systems. Glial cells are increasingly recognized as key contributors to neurodegenerative disease progression through non-cell autonomous mechanisms. Planarians possess a nervous system with diverse neuronal subtypes and glial cells, offering an attractive combination of evolutionary conservation and remarkable regenerative capacity. Unlike mammalian glia, planarian glia originate from phagocytic progenitors and exhibit distinctive molecular markers, including if-1, cali and cathepsin. Emerging evidence suggests that planarian glia may contribute to neurotransmitter homeostasis, neuron–glia interactions and phagocytic activity. Additionally, planarians display robust and quantifiable behavioral responses, making them well suited for modeling neurodegenerative disease. In this review, we summarize the current findings regarding neuronal subtypes and glial cells in planaria, emphasizing their relevance as a model system. Further research into planarian glia will be crucial for understanding their roles in pathological contexts and for exploring their potential applications in neurodegenerative diseases research. Planarian simplicity, regenerative capacity, and compatibility with high-throughput approaches position planarians as a powerful model for investigating the cellular and molecular mechanisms underlying neurodegenerative diseases and for identifying potential therapeutic targets.