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Search Results: 1 - 10 of 744 matches for " Yuzuru Imai "
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Mitochondrial Regulation by PINK1-Parkin Signaling
Yuzuru Imai
ISRN Cell Biology , 2012, DOI: 10.5402/2012/926160
Abstract:
Mitochondrial Regulation by PINK1-Parkin Signaling
Yuzuru Imai
ISRN Cell Biology , 2012, DOI: 10.5402/2012/926160
Abstract: Two genes responsible for the juvenile Parkinson’s disease (PD), PINK1 and Parkin, have been implicated in mitochondrial quality control. The inactivation of PINK1, which encodes a mitochondrial kinase, leads to age-dependent mitochondrial degeneration in Drosophila. The phenotype is closely associated with the impairment of mitochondrial respiratory chain activity and defects in mitochondrial dynamics. Drosophila genetic studies have further revealed that PINK1 is an upstream regulator of Parkin and is involved in the mitochondrial dynamics and motility. A series of cell biological studies have given rise to a model in which the activation of PINK1 in damaged mitochondria induces the selective elimination of mitochondria in cooperation with Parkin through the ubiquitin-proteasome and autophagy machineries. Although the relevance of this pathway to PD etiology is still unclear, approaches using stem cells from patients and animal models will help to understand the significance of mitochondrial quality control by the PINK1-Parkin pathway in PD and in healthy individuals. Here I will review recent advances in our understanding of the PINK1-Parkin signaling and will discuss the roles of PINK1-Parkin signaling for mitochondrial maintenance and how the failure of this signaling leads to neurodegeneration. 1. Introduction While eukaryotic cells have acquired the highly efficient power-generating system of aerobic respiration by incorporating mitochondria into the cytosol, they can suffer from problems related to uncontrollable oxidization. Nondividing cells or tissues with high energy demands in long-living animals require countermeasures against this issue because mitochondrial dysregulation has been implicated as one cause of neurodegeneration. The neuropathology of Parkinson’s disease, the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the degeneration of dopaminergic neurons in the midbrain. Mitochondrial dysfunction has long been a suspected cause of PD because the Parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is as a selective inhibitor of mitochondrial complex I. Reduced complex I activity has also been reported in autopsied brains and platelets from patients with sporadic PD [1–3], while mutations or polymorphisms in mitochondrial DNA are implicated in the genetic risk for PD [4]. Animals treated with a variety of mitochondrial toxins, including MPTP, 6-hydroxy-dopamine (6-OHDA), rotenone, and paraquat, partly recapitulate PD pathology, suggesting that mitochondrial
Animal Models of Parkinson's Disease
Yuzuru Imai,Katerina Venderova,David S. Park,Huaibin Cai
Parkinson's Disease , 2011, DOI: 10.4061/2011/364328
Abstract:
Animal Models of Parkinson's Disease 2012
Yuzuru Imai,Katerina Venderova,Kah-Leong Lim
Parkinson's Disease , 2012, DOI: 10.1155/2012/729428
Abstract:
Animal Models of Parkinson's Disease 2012
Yuzuru Imai,Katerina Venderova,Kah-Leong Lim
Parkinson's Disease , 2012, DOI: 10.1155/2012/729428
Abstract:
PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in Drosophila
Kahori Shiba-Fukushima,Tsuyoshi Inoshita,Nobutaka Hattori ,Yuzuru Imai
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004391
Abstract: Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. We have reported that Parkin is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian cultured cells. However, it remains unclear whether Parkin phosphorylation is involved in mitochondrial maintenance and activity of dopaminergic neurons in vivo. Here, we examined the effects of Parkin phosphorylation in Drosophila, in which the phosphorylation residue is conserved at Ser94. Morphological changes of mitochondria caused by the ectopic expression of wild-type Parkin in muscle tissue and brain dopaminergic neurons disappeared in the absence of PINK1. In contrast, phosphomimetic Parkin accelerated mitochondrial fragmentation or aggregation and the degradation of mitochondrial proteins regardless of PINK1 activity, suggesting that the phosphorylation of Parkin boosts its ubiquitin-ligase activity. A non-phosphorylated form of Parkin fully rescued the muscular mitochondrial degeneration due to the loss of PINK1 activity, whereas the introduction of the non-phosphorylated Parkin mutant in Parkin-null flies led to the emergence of abnormally fused mitochondria in the muscle tissue. Manipulating the Parkin phosphorylation status affected spontaneous dopamine release in the nerve terminals of dopaminergic neurons, the survivability of dopaminergic neurons and flight activity. Our data reveal that Parkin phosphorylation regulates not only mitochondrial function but also the neuronal activity of dopaminergic neurons in vivo, suggesting that the appropriate regulation of Parkin phosphorylation is important for muscular and dopaminergic functions.
Animal Models of Parkinson's Disease
Yuzuru Imai,Katerina Venderova,David S. Park,Huaibin Cai,Enrico Schmidt
Parkinson's Disease , 2011, DOI: 10.4061/2011/364328
Abstract:
The Nitric Oxide-Cyclic GMP Pathway Regulates FoxO and Alters Dopaminergic Neuron Survival in Drosophila
Tomoko Kanao, Tomoyo Sawada, Shireen-Anne Davies, Hiroshi Ichinose, Kazuko Hasegawa, Ryosuke Takahashi, Nobutaka Hattori, Yuzuru Imai
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030958
Abstract: Activation of the forkhead box transcription factor FoxO is suggested to be involved in dopaminergic (DA) neurodegeneration in a Drosophila model of Parkinson's disease (PD), in which a PD gene product LRRK2 activates FoxO through phosphorylation. In the current study that combines Drosophila genetics and biochemical analysis, we show that cyclic guanosine monophosphate (cGMP)-dependent kinase II (cGKII) also phosphorylates FoxO at the same residue as LRRK2, and Drosophila orthologues of cGKII and LRRK2, DG2/For and dLRRK, respectively, enhance the neurotoxic activity of FoxO in an additive manner. Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site in the same manner as LRRK2. A Drosophila FoxO mutant resistant to phosphorylation by DG2 and dLRRK (dFoxO S259A corresponding to human FoxO1 S319A) suppressed the neurotoxicity and improved motor dysfunction caused by co-expression of FoxO and DG2. Nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) also increased FoxO's activity, whereas the administration of a NOS inhibitor L-NAME suppressed the loss of DA neurons in aged flies co-expressing FoxO and DG2. These results strongly suggest that the NO-FoxO axis contributes to DA neurodegeneration in LRRK2-linked PD.
Trochanteric Fracture of a Congenital/Developmental Dislocation of the Hip in an Elderly Woman: A Case Report  [PDF]
Kazuhiro Imai
Open Journal of Orthopedics (OJO) , 2011, DOI: 10.4236/ojo.2011.11001
Abstract: An 87-year-old woman with a residual dislocated hip suffered a trochanteric fracture on the ipsilateral side. The fracture was treated by open reduction and internal fixation surgery with good results. To treat a proximal femoral fracture of the residual dislocated hip in an elderly patient, the patient’s overall status, pre-fracture ability, hip joint configuration, and fracture pattern should be considered.
In Vivo Investigation of Zr-Based Bulk Metallic Glasses Sub-Periosteally Implanted on the Bone Surface  [PDF]
Kazuhiro Imai
Journal of Materials Science and Chemical Engineering (MSCE) , 2016, DOI: 10.4236/msce.2016.41009
Abstract:

Bulk metallic glasses (BMG) show higher strength and lower Young’s modulus than SUS 316L stainless steel and Ti-6Al-4V alloys. This study aimed to investigate the reaction of Zr-based BMG sub-periosteally implanted on the surface of the rat femur, thereby evaluate the possibility of the BMG as biomaterials for osteosynthetic devices. Zr65Al7.5Ni10Cu17.5 BMG ribbons with 10 mm length, 2 mm width and 0.5 mm thickness were implanted sub-periosteally on the femur surface in three male Wistar rats for 6 weeks. Systemic effects were evaluated by measuring Cu and Ni levels in the blood, and local effects were evaluated by the histological observation of the surrounding soft tissues in contact with the BMG. The reaction of the surface of the BMG was examined with scanning electron microscopy. No increase of Cu and Ni levels in the blood was recognized. In the scanning electron microscopy observation, spherical deposits which were considered as sodium chloride crystals were observed. Neither breakage nor pitting corrosion was noted. BMG will be a promising metallic biomaterial for osteosynthetic device that must be removed.

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