Mutation Analysis of the PINK1 Gene in 391 Patients With Parkinson Disease

Kumazawa, Ryuya; Tomiyama, Hiroyuki; Li, Yuanzhe; Imamichi, Yoko; Funayama, Manabu; Yoshino, Hideaki; Yokochi, Fusako; Fukusako, T; Takehisa, Yasushi; Kashihara, Kenichi; Kondo, Tomoyoshi; Elibol, Bülent; Bostantjopoulou, Sevasti; Toda, Tatsushi; Takahashi, Hirohide; Yoshii, Fumihito; Mizuno, Yoshikuni; Hattori, Nobutaka

doi:10.1001/archneur.65.6.802

Cited by 82 publications

(56 citation statements)

References 30 publications

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“…More than 50 mutations in the PINK1 gene (1p36), located at the PARK6 locus, have been identified in PD-affected patients [239][240][241][242][243] and these mutations are believed to account for up to 1-8 % of sporadic cases with early onset [244].…”

Section: Pink1 (Park6)mentioning

confidence: 99%

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Grand

Gonzalez-Cano

Pavlou

et al. 2014

Cell. Mol. Life Sci.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to a variety of motor and non-motor symptoms. Interestingly, nonmotor symptoms often appear a decade or more before the first signs of motor symptoms. Some of these non-motor symptoms are remarkably similar to those observed in cases of impaired neurogenesis and several PD-related genes have been shown to play a role in embryonic or adult neurogenesis. Indeed, animal models deficient in Nurr1, Pitx3, SNCA and PINK1 display deregulated embryonic neurogenesis and LRRK2 and VPS35 have been implicated in neuronal development-related processes such as Wnt/bcatenin signaling and neurite outgrowth. Moreover, adult neurogenesis is affected in both PD patients and PD animal models and is regulated by dopamine and dopaminergic (DA) receptors, by chronic neuroinflammation, such as that observed in PD, and by differential expression of wild-type or mutant forms of PD-related genes. Indeed, an increasing number of in vivo studies demonstrate a role for SNCA and LRRK2 in adult neurogenesis and in the generation and maintenance of DA neurons. Finally, the roles of PDrelated genes, SNCA, LRRK2, VPS35, Parkin, PINK1 and DJ-1 have been studied in NSCs, progenitor cells and induced pluripotent stem cells, demonstrating a role for some of these genes in stem/progenitor cell proliferation and maintenance. Together, these studies strongly suggest a link between deregulated neurogenesis and the onset and progression of PD and present strong evidence that, in addition to a neurodegenerative disorder, PD can also be regarded as a developmental disorder.

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Section: Pink1 (Park6)mentioning

confidence: 99%

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Grand

Gonzalez-Cano

Pavlou

et al. 2014

Cell. Mol. Life Sci.

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“…3) and the dissimilarity index of the change [Majewski and Ott, 2003], suggest that mutations E240K, P296L, L369P, G440E, L461S, and W437R cause the more drastic effects. These predictions, coupled to our structural analysis, allow us to propose the bigger deleterious effect for L369P and W437R, two mutations that are apparently able to produce the disease when present in heterozygosity [Ibanez et al, 2006;Kumazawa et al, 2008].…”

Section: Structural Consequences Of Pink1 Pd-associated Mutationsmentioning

confidence: 99%

Phylogenetic and in silico structural analysis of the Parkinson disease‐related kinase PINK1

et al. 2011

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Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Mutations in PINK1 were shown to cause recessive familial PD, and today are proposed to be associated with the disease via mitochondrial dysfunction and oxidative damage. The PINK1 gene comprises eight exons, which encode a ubiquitously expressed 581 amino acid protein that contains an N-terminal mitochondrial targeting domain and a serine/threonine protein kinase. To better understand the relationship between PINK1 and PD we have first analyzed the evolutionary history of the gene showing its late emergence in evolution. In addition, we have modeled the three-dimensional structure of PINK1 and found some evidences that help to explain the effect of some PD-related mutations in this protein's function.

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“…Most of the previous studies on PINK1 gene variations focussed on their association with Parkinson's disease (Toft et al 2007;Kumazawa et al 2008;Brooks et al 2009). Due to few previous studies on the association of genetic variation in PINK1 gene with T2DM, only a few other groups provided indirect evidences on the role of PINK1 gene in the development of T2DM.…”

Section: Pink1 Gene Variation Associated With Type 2 Diabetesmentioning

confidence: 99%

Variation in the PTEN-induced putative kinase 1 gene associated with the increase risk of type 2 diabetes in northern Chinese

Sun

Yang

et al. 2011

J Genet

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Mutation Analysis of the PINK1 Gene in 391 Patients With Parkinson Disease

Cited by 82 publications

References 30 publications

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Phylogenetic and in silico structural analysis of the Parkinson disease‐related kinase PINK1

Variation in the PTEN-induced putative kinase 1 gene associated with the increase risk of type 2 diabetes in northern Chinese

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