Novel insights into Parkin-mediated mitochondrial dysfunction and neuroinflammation in Parkinson's disease |
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| Affiliation: | 1. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg;2. Translational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany;3. Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock/Greifswald, 18147 Rostock, Germany;4. Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany;5. Institute of Neurogenetics, University of Lübeck, Lübeck, Germany |
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| Abstract: | Mutations in PRKN cause the second most common genetic form of Parkinson's disease (PD)—a debilitating movement disorder that is on the rise due to population aging in the industrial world. PRKN codes for an E3 ubiquitin ligase that has been well established as a key regulator of mitophagy. Together with PTEN-induced kinase 1 (PINK1), Parkin controls the lysosomal degradation of depolarized mitochondria. But Parkin's functions go well beyond mitochondrial clearance: the versatile protein is involved in mitochondria-derived vesicle formation, cellular metabolism, calcium homeostasis, mitochondrial DNA maintenance, mitochondrial biogenesis, and apoptosis induction. Moreover, Parkin can act as a modulator of different inflammatory pathways. In the current review, we summarize the latest literature concerning the diverse roles of Parkin in maintaining a healthy mitochondrial pool. Moreover, we discuss how these recent discoveries may translate into personalized therapeutic approaches not only for PRKN-PD patients but also for a subset of idiopathic cases. |
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| Keywords: | Parkin Parkinson's disease Mitochondria mtDNA Metabolism Inflammation Mitophagy Calcium PINK1 Biogenesis BAK" },{" #name" :" keyword" ," $" :{" id" :" pc_gMMXR0ZAa3" }," $$" :[{" #name" :" text" ," _" :" BCL2-antagonist/killer 1 BAX" },{" #name" :" keyword" ," $" :{" id" :" pc_BUF5wF4U3F" }," $$" :[{" #name" :" text" ," _" :" Bcl-2-associated X protein ccf" },{" #name" :" keyword" ," $" :{" id" :" pc_2BpW1jwSVR" }," $$" :[{" #name" :" text" ," _" :" circulating cell-free cGAS" },{" #name" :" keyword" ," $" :{" id" :" pc_nybseJK51I" }," $$" :[{" #name" :" text" ," _" :" cyclic GMP–AMP synthase mtDNA" },{" #name" :" keyword" ," $" :{" id" :" pc_tdCqEnFMB5" }," $$" :[{" #name" :" text" ," _" :" mitochondrial DNA MERCS" },{" #name" :" keyword" ," $" :{" id" :" pc_cdW2MJc4mt" }," $$" :[{" #name" :" text" ," _" :" mitochondria-ER contact sites mitoDAMPs" },{" #name" :" keyword" ," $" :{" id" :" pc_HNlNxZlxzN" }," $$" :[{" #name" :" text" ," _" :" mitochondrial damage-associated molecular patterns MCU" },{" #name" :" keyword" ," $" :{" id" :" pc_FkIRrVBop4" }," $$" :[{" #name" :" text" ," _" :" mitochondrial calcium uptake MDVs" },{" #name" :" keyword" ," $" :{" id" :" pc_NTpW3vGXLJ" }," $$" :[{" #name" :" text" ," _" :" mitochondrial-derived vesicles MFN" },{" #name" :" keyword" ," $" :{" id" :" pc_ICPKLaI9BQ" }," $$" :[{" #name" :" text" ," _" :" Mitofusin NLRP3" },{" #name" :" keyword" ," $" :{" id" :" pc_P1IPupQucR" }," $$" :[{" #name" :" text" ," _" :" NLR family pyrin domain containing 3 OPTN" },{" #name" :" keyword" ," $" :{" id" :" pc_CII25AhdM7" }," $$" :[{" #name" :" text" ," _" :" Optineurin PARIS" },{" #name" :" keyword" ," $" :{" id" :" pc_hwWYWLSfHl" }," $$" :[{" #name" :" text" ," _" :" Parkin-interacting substrate PRKN" },{" #name" :" keyword" ," $" :{" id" :" pc_hHrKoFaKp9" }," $$" :[{" #name" :" text" ," _" :" Parkin PINK1" },{" #name" :" keyword" ," $" :{" id" :" pc_BJiznAwWuN" }," $$" :[{" #name" :" text" ," _" :" PTEN induced kinase 1 PGC-1a" },{" #name" :" keyword" ," $" :{" id" :" pc_zsPUIrKoln" }," $$" :[{" #name" :" text" ," _" :" peroxisome proliferator-activated receptor-gamma coactivator 1 alpha POLG" },{" #name" :" keyword" ," $" :{" id" :" pc_Vfrydsj0kY" }," $$" :[{" #name" :" text" ," _" :" mitochondrial polymerase gamma PD" },{" #name" :" keyword" ," $" :{" id" :" pc_6UXnE0gVMx" }," $$" :[{" #name" :" text" ," _" :" Parkinson’s disease SIRT1" },{" #name" :" keyword" ," $" :{" id" :" pc_SCBAUfkAwr" }," $$" :[{" #name" :" text" ," _" :" Sirtuin 1 SN" },{" #name" :" keyword" ," $" :{" id" :" pc_HJ9Xj8Wu14" }," $$" :[{" #name" :" text" ," _" :" substantia nigra STING" },{" #name" :" keyword" ," $" :{" id" :" pc_ZkqHlEhhzU" }," $$" :[{" #name" :" text" ," _" :" stimulator of interferon genes TOM" },{" #name" :" keyword" ," $" :{" id" :" pc_8bQGeSTRF0" }," $$" :[{" #name" :" text" ," _" :" translocase of the outer membrane TBK1" },{" #name" :" keyword" ," $" :{" id" :" pc_RNSnJNyhNH" }," $$" :[{" #name" :" text" ," _" :" TANK-binding kinase 1 ULK1" },{" #name" :" keyword" ," $" :{" id" :" pc_oiZcvEbG9e" }," $$" :[{" #name" :" text" ," _" :" unc-51-like autophagy activating kinase 1 VDAC1" },{" #name" :" keyword" ," $" :{" id" :" pc_OyNzs23PGv" }," $$" :[{" #name" :" text" ," _" :" voltage-dependent anion-selective channel 1 |
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