Direct Reprogramming of Somatic Cells to Neurons: Pros and Cons of Chemical Approach

Translating successful preclinical research in neurodegenerative diseases into clinical practice has been difficult. The preclinical disease models used for testing new drugs not always appear predictive of the effects of the agents in the human disease state. Human induced pluripotent stem cells, obtained by reprogramming of adult somatic cells, represent a powerful system to study the molecular mechanisms of the disease onset and pathogenesis. However, these cells require a long time to differentiate into functional neural cells and the resetting of epigenetic information during reprogramming, might miss the information imparted by age. On the contrary, the direct conversion of somatic cells to neuronal cells is much faster and more efficient, it is safer for cell therapy and allows to preserve the signatures of donors’ age. Direct reprogramming can be induced by lineage-specific transcription factors or chemical cocktails and represents a powerful tool for modeling neurological diseases and for regenerative medicine. In this Commentary we present and discuss strength and weakness of several strategies for the direct cellular reprogramming from somatic cells to generate human brain cells which maintain age‐related features. In particular, we describe and discuss chemical strategy for cellular reprogramming as it represents a valuable tool for many applications such as aged brain modeling, drug screening and personalized medicine.