Cargando…
Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease
Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized 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 caus...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373244/ https://www.ncbi.nlm.nih.gov/pubmed/32714578 http://dx.doi.org/10.1042/NS20170027 |
_version_ | 1783561464486821888 |
---|---|
author | O'Keeffe, Gerard W. Hegarty, Shane V. Sullivan, Aideen M. |
author_facet | O'Keeffe, Gerard W. Hegarty, Shane V. Sullivan, Aideen M. |
author_sort | O'Keeffe, Gerard W. |
collection | PubMed |
description | Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized 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 that 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 BMP ligands, BMP 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. |
format | Online Article Text |
id | pubmed-7373244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73732442020-07-23 Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease O'Keeffe, Gerard W. Hegarty, Shane V. Sullivan, Aideen M. Neuronal Signal Review Articles Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized 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 that 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 BMP ligands, BMP 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. Portland Press Ltd. 2017-03-31 /pmc/articles/PMC7373244/ /pubmed/32714578 http://dx.doi.org/10.1042/NS20170027 Text en © 2017 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
spellingShingle | Review Articles O'Keeffe, Gerard W. Hegarty, Shane V. Sullivan, Aideen M. Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease |
title | Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease |
title_full | Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease |
title_fullStr | Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease |
title_full_unstemmed | Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease |
title_short | Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease |
title_sort | targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in parkinson's disease |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373244/ https://www.ncbi.nlm.nih.gov/pubmed/32714578 http://dx.doi.org/10.1042/NS20170027 |
work_keys_str_mv | AT okeeffegerardw targetingbonemorphogeneticproteinsignallinginmidbraindopaminergicneuronsasatherapeuticapproachinparkinsonsdisease AT hegartyshanev targetingbonemorphogeneticproteinsignallinginmidbraindopaminergicneuronsasatherapeuticapproachinparkinsonsdisease AT sullivanaideenm targetingbonemorphogeneticproteinsignallinginmidbraindopaminergicneuronsasatherapeuticapproachinparkinsonsdisease |