Abstract

Parkinson's disease is the second most common neurodegenerative disorder; it affects 1% of the population over the age of 65. The number of people with Parkinson's disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying therapies. The pathological hallmarks of Parkinson's disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum, and the aggregation of α-synuclein; these result in a range of debilitating motor and non-motor symptoms. The application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research interest. However, this strategy has had limited success to date. Clinical trials of two well-known neurotrophic factors, glial cell line-derived neurotrophic factor and neurturin, have reported limited efficacy in Parkinson's disease patients, despite these factors showing potent neurotrophic actions in animal studies. There is therefore a need to identify other neurotrophic factors that can protect against α-synuclein-induced degeneration of dopaminergic neurons. The bone morphogenetic protein (BMP) family is the largest subgroup of the transforming growth factor-β superfamily of proteins. BMPs are naturally secreted proteins that play crucial roles throughout the developing nervous system. Importantly, many BMPs have been shown to be potent neurotrophic factors for dopaminergic neurons. Here we discuss recent work showing that transcripts for the BMP receptors and BMP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra, and evidence for downregulation of BMP2 expression at distinct stages of Parkinson's disease. We also discuss studies that explored the effects of BMP2 treatment, in in vitro and in vivo models of Parkinson's disease. These studies found potent effects of BMP2 on dopaminergic neurites, which is important given that axon degeneration is increasingly recognized as a key early event in Parkinson's disease. Thus, the aim of this mini-review is to give an overview of the BMP family and the BMP-Smad signalling pathway, in addition to reviewing the available evidence demonstrating the potential of BMP2 for Parkinson's disease therapy.

Disciplines

Biology | Life Sciences | Neuroscience and Neurobiology

DOI

10.4103/1673-5374.274327

Full Publication Date

January 2020

Publication Details

Neural Regeneration Research.

© 2020 Wolters Kluwer Medknow Publications.

Publisher

Wolters Kluwer Medknow Publications

Funder Name 1

Cork Institute of Technology

Award Number 1

R00094948

Funder Name 2

Science Foundation Ireland

Award Number 2

15/CDA/3498

Resource Type

review

Access Rights

open access

Alternative Identifier

http://www.nrronline.org/text.asp?2020/15/8/1432/274327

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