PINK1 and Its Familial Parkinson's Disease-Associated Mutation Regulate Brain Vascular Endothelial Inflammation

Wang, Yunfu; Liu, Guangjian; Zhong, Ping; Sun, Yu; Fang, Xiao-Xia; Wei, Haoyan; Yuan, Junfa; Jingquan, Hu; Wang, Songlin; Zhang, Hongyan; Liu, Yong; Shi, Chen

doi:10.1007/s12031-013-0207-1

Cited by 14 publications

(11 citation statements)

References 22 publications

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“…One such example was found in a recent publication that showed an effect of PINK1 on the regulation of the expression of the TF IRF1 (Yunfu et al ., ). Endothelial dysfunction, particularly that of the blood–brain barrier, has been found to be involved in neurodegenerative diseases, and one of the earliest events in endothelial inflammation is the expression of adhesion molecules such as VCAM1 on the cell surface.…”

Section: Bioinformatics Analysis To Identify Common Transcription Facmentioning

confidence: 97%

“…Furthermore, IRF1 expression accounts for the inflammatory upregulation of VCAM1 during transcription (Sun et al ., ). It was found that expression of wild‐type PINK1 inhibited the induction of VCAM1 and decreased the expression of nuclear IRF1, whereas overexpression of mutant PINK1 increased IRF1 and VCAM1 expression (Yunfu et al ., ). These results suggest that PINK1 regulates endothelial inflammation through activation of the IRF1 pathway.…”

Section: Bioinformatics Analysis To Identify Common Transcription Facmentioning

confidence: 97%

“…Future studies such as the one by Yunfu et al . () are therefore vital in the understanding of the role of these three proteins on the expression and regulation of TFs and vice versa.…”

Section: Bioinformatics Analysis To Identify Common Transcription Facmentioning

confidence: 99%

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Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1

Merwe

Dashti

Christoffels

et al. 2015

Eur J of Neuroscience

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Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the midbrain. Autosomal recessive, early-onset cases of PD are predominantly caused by mutations in the parkin, PINK1 and DJ-1 genes. Animal and cellular models have verified a direct link between parkin and PINK1, whereby PINK1 phosphorylates and activates parkin at the outer mitochondrial membrane, resulting in removal of dysfunctional mitochondria via mitophagy. Despite the overwhelming evidence for this interaction, few studies have been able to identify a link for DJ-1 with parkin or PINK1. The aim of this review is to summarise the functions of these three proteins, and to analyse the existing evidence for direct and indirect interactions between them. DJ-1 is able to rescue the phenotype of PINK1-knockout Drosophila models, but not of parkin-knockouts, suggesting that DJ-1 may act in a parallel pathway to that of the PINK1/parkin pathway. To further elucidate a commonality between these three proteins, bioinformatics analysis established that Miro (RHOT1) interacts with parkin and PINK1, and HSPA4 interacts with all three proteins. Furthermore, 30 transcription factors were found to be common amongst all three proteins, with many of them being involved in transcriptional regulation. Interestingly, expression of these proteins and their associated transcription factors are found to be significantly down-regulated in PD patients compared to healthy controls. In summary, this review provides insight into common pathways linking three PD-causing genes and highlights some key questions, the answers to which may provide critical insight into the disease process.

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Section: Bioinformatics Analysis To Identify Common Transcription Facmentioning

confidence: 97%

Section: Bioinformatics Analysis To Identify Common Transcription Facmentioning

confidence: 97%

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Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1

Merwe

Dashti

Christoffels

et al. 2015

Eur J of Neuroscience

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“…One of major breakthroughs in PD research was the discovery of the close association between PINK1 and autosomal recessive familial Parkinson’s disease [8,9]. In healthy mitochondria, PINK1 protects cells from damage-induced mitochondrial dysfunction, oxidative stress and cell apoptosis [10].…”

Section: Introductionmentioning

confidence: 99%

Cytoprotection against Hypoxic and/or MPP+ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3

Zhi

Shao

et al. 2016

IJMS

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The pathological changes of Parkinson’s disease (PD) are, at least partially, associated with the dysregulation of PTEN-induced putative kinase 1 (PINK1) and caspase 3. Since hypoxic and neurotoxic insults are underlying causes of PD, and since δ-opioid receptor (DOR) is neuroprotective against hypoxic/ischemic insults, we sought to determine whether DOR activation could protect the cells from damage induced by hypoxia and/or MPP+ by regulating PINK1 and caspase 3 expressions. We exposed PC12 cells to either severe hypoxia (0.5%–1% O2) for 24–48 h or to MPP+ at different concentrations (0.5, 1, 2 mM) and then detected the levels of PINK1 and cleaved caspase 3. Both hypoxia and MPP+ reduced cell viability, progressively suppressed the expression of PINK1 and increased the cleaved caspase 3. DOR activation using UFP-512, effectively protected the cells from hypoxia and/or MPP+ induced injury, reversed the reduction in PINK1 protein and significantly attenuated the increase in the cleaved caspase 3. On the other hand, the application of DOR antagonist, naltrindole, greatly decreased cell viability and increased cleaved caspase 3. These findings suggest that DOR is cytoprotective against both hypoxia and MPP+ through the regulation of PINK1 and caspase 3 pathways.

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“…PINK1 is an important gene that was initially discovered to be mutated in early‐onset parkinsonism . Normal PINK1 expression and function are important for the brain, while functional loss or dysregulation of PINK1 may exhibit similar symptoms as seen in PD . The PINK1 gene encodes a 581 amino acid protein, and the protein sequence reveals a C‐terminal kinase domain and a N‐terminal mitochondrial targeting domain, suggesting its close linkage to mitochondria.…”

Section: Potential Mechanisms For Dor Protection Against Pdmentioning

confidence: 99%

The delta‐opioid receptor and Parkinson’s disease

Huang

Ren

et al. 2018

CNS Neurosci Ther

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Parkinson's disease (PD) is a common degenerative neurological disease leading to a series of familial, medical, and social problems. Although it is known that the major characteristics of PD pathophysiology are the dysfunction of basal ganglia due to injury/loss of dopaminergic neurons in the substantia nigra pars compacta dopaminergic and exhaustion of corpus striatum dopamine, therapeutic modalities for PD are limited in clinical settings up to date. It is of utmost importance to better understand PD pathophysiology and explore new solutions for this serious neurodegenerative disorder. Our recent work and those of others suggest that the delta-opioid receptor (DOR) is neuroprotective and serves an antiparkinsonism role in the brain. This review summarizes recent progress in this field and explores potential mechanisms for DOR-mediated antiparkinsonism.

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PINK1 and Its Familial Parkinson's Disease-Associated Mutation Regulate Brain Vascular Endothelial Inflammation

Cited by 14 publications

References 22 publications

Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1

Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1

Cytoprotection against Hypoxic and/or MPP+ Injury: Effect of δ–Opioid Receptor Activation on Caspase 3

The delta‐opioid receptor and Parkinson’s disease

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