Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection.
Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death-through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection.
The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK.
Uma A
UA
Mukherjee
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
Sang-Bing
SB
Ong
Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, USA.
Sang-Ging
SG
Ong
The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK; Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, UK. Electronic address: derek.hausenloy@duke-nus.edu.sg.
Derek J
DJ
Hausenloy
D002316:Cardiotonic Agents / Q000494:pharmacology; D016923:Cell Death; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D002316:Cardiotonic Agents; D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human
Coronary heart disease; Parkinson’s disease; ischaemic preconditioning; mitochondria; myocardial ischaemia-reperfusion injury