Parkinson's disease (PD) is the second most common neurodegenerative disease, characterised by the degeneration of midbrain dopaminergic (mDA) neurons and their axons, and aggregation of α-synuclein, which leads to motor and late-stage cognitive impairments. As the motor symptoms of PD are caused by the degeneration of a specific population of mDA neurons, PD lends itself to neurotrophic factor therapy. The goal of this therapy is to apply a neurotrophic factor which can slow down, halt or even reverse the progressive degeneration of mDA neurons. While the best known neurotrophic factors are members of the glial cell-line derived neurotrophic factor (GDNF) family, their lack of clinical efficacy to date means that it is important to continue to study other neurotrophic factors. Bone morphogenetic proteins (BMPs) are naturally secreted proteins that play critical roles during nervous system development and in the adult brain. In this review we provide an overview of the BMPs ligands, receptors (BMPRs) and their intracellular signalling effectors, the Smad proteins. We review the available evidence that BMP-Smad signalling pathways play an endogenous role in mDA neuronal survival in vivo , before outlining how exogenous application of BMPs exerts potent effects on mDA neuron survival and axon growth in vitro and in vivo . We discuss the molecular mechanisms that mediate these effects, before highlighting the potential of targeting the downstream effectors of BMP-Smad signalling as a novel neuroprotective approach to slow or stop the degeneration of mDA neurons in PD.
- Parkinsons disease
- Bone morphogenetic protein
- neurotrophic factors
- Received September 28, 2016.
- Revision received February 20, 2017.
- Accepted February 23, 2017.
- ©2017 The Author(s)
This is an Accepted Manuscript; not the final Version of Record. You are encouraged to use the final Version of Record that, when published, will replace this manuscript and be freely available under a Creative Commons licence.