Regulation of bdnf‐trkb signaling and potential therapeutic strategies for parkinson’s disease

Abstract

Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin‐related kinase receptor type B (TrkB) are widely distributed in multiple regions of the human brain. Specifically, BDNF/TrkB is highly expressed and activated in the dopaminergic neurons of the substantia nigra and plays a critical role in neurophysiological processes, including neuro‐protection and maturation and maintenance of neurons. The activation as well as dysfunction of the BDNF‐TrkB pathway are associated with neurodegenerative diseases. The expression of BDNF/TrkB in the substantia nigra is significantly reduced in Parkinson’s Disease (PD) patients. This review summarizes recent progress in the understanding of the cellular and molecular roles of BNDF/TrkB signaling and its isoform, TrkB.T1, in Parkinson’s disease. We have also discussed the effects of current therapies on BDNF/TrkB signaling in Parkinson’s disease patients and the mechanisms underlying the mutationmediated acquisition of resistance to therapies for Parkinson’s disease.