Neuroscience: Restoring lost brain cells in neurodegenerative disease

A single-step method to convert non-neuronal brain cells into functional neurons, demonstrated in isolated human cells and in mice, is reported in Nature this week. The technique is shown to reverse symptoms of Parkinson’s disease in a mouse model of the disease, and may represent a new approach to explore for the treatment of neurodegenerative conditions./p>

A major goal of regenerative medicine is to replace neurons lost during neurodegenerative disorders and promote integration of new neurons into functional neural circuits. Parkinson’s disease, for example, is characterized by a loss of dopaminergic neurons in a region of the brain responsible for reward and movement.

Xiang-Dong Fu and colleagues show that astrocytes can be turned into functional dopaminergic neurons. Astrocytes are non-neuronal brain cells that produce an RNA-binding protein called PTBP1, which prevents them from becoming neurons. Removing PTBP1 converts them to fully functional neurons that repopulate the lost neuronal circuits, restores dopamine levels and rescues motor deficits in mouse models of Parkinson’s disease, the authors report. Importantly, transiently suppressing PTBP1 with antisense oligonucleotides, a class of therapeutic that has recently demonstrated remarkable promise in the treatment of neurodegenerative diseases, is also effective.

The study offers a new regenerative approach for the treatment of neurodegenerative diseases. The authors caution that further research is needed before the approach can be applied to humans. Once developed further, it may be applicable not only to Parkinson’s disease but also other neurodegenerative disorders.