The promise of the TGF-β superfamily as a therapeutic target for Parkinson's disease

A large body of evidence underscore the regulatory role of TGF-β superfamily in the central nervous system. Components of the TGF-β superfamily modulate key events during embryonic brain development and adult brain tissue injury repair. With respect to Parkinson's disease (PD), TGF-ß signaling pathways are implicated in the differentiation, maintenance and synaptic function of the dopaminergic neurons, as well as in processes related to the activation state of astrocytes and microglia. In vitro and in vivo studies using toxin models, have interrogated on the dopaminotrophic and protective role of the TGF-β superfamily members. The evolution of genetic and animal models of PD that more closely recapitulate the disease condition has made possible the dissection of intracellular pathways in response to TGF-β treatment. Although the first clinical trials using GDNF did not meet their primary endpoints, substantial work has been carried out to reappraise the TGF-β superfamily's clinical benefit.