Neurotrophic factors hold promise for the future of Parkinson's disease treatment: is there a light at the end of the tunnel?

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by a spectrum of clinicopathologic signs and a complex etiology. PD results from the degeneration of dopaminergic (DAergic) neurons in the substantia nigra. Current therapies for PD are only able to alleviate symptoms without stopping disease progression. In addition, the available therapeutic strategies do not have long-lasting effects. Furthermore, these therapies cause different ranges of adverse side effects. There is great interest in neurotrophic factors (NTFs) due to their ability to promote the survival of different neural cells. These factors are divided into four families: neurotrophins, neurokines, the glial cell line-derived NTF family of ligands, and the newly recognized cerebral DA NTF/mesencephalic astrocyte-derived NTF family. The protective and therapeutic effects of these factors on DAergic neurons make them suitable for the prevention of progressive cell loss in PD. Based on the above premise, we focus on the protective effects of NTFs, especially CDNF and MANF, on nigrostriatal DAergic neurons in PD.