Programmed cell death‐2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease

Fukae, Jiro; Sato, Shigeto; Shiba, Kahori; Sato, Kenichi; Mori, Hideo; Sharp, Philip A.; Mizuno, Yoshikuni

doi:10.1016/j.febslet.2008.12.055

Cited by 31 publications

(20 citation statements)

References 14 publications

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“…Regulates LRRK2 stability [24] and ubiquinates α-synuclein [76] PDCD2 Programmed cell death 2 Ubiquitinated by PARKIN [77] SNCAIP/synphilin-1 Synuclein, α-interacting protein Inhibits α-synuclein degradation by the proteasome [78] and enhances its aggregation [79] SLC6A3 Solute carrier family 6-dopamine transporter Critical for dopamine neurotransmission…”

Section: Expert Commentarymentioning

confidence: 99%

Network modeling to identify new mechanisms and therapeutic targets for Parkinson’s disease

MacArthur

Ressom

Shah

et al. 2013

Expert Review of Neurotherapeutics

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Biomolecules in subnetworks are the focus of a new strategy to develop drugs that halt complex diseases. In this article, the authors use genome-wide association study and linkage data derived from Parkinson's disease studies to illustrate how algorithms that use gene and protein interaction databases reveal subnetworks in biological systems that suggest mechanisms for disease progression. Network modeling may help develop testable hypotheses for neurodegenerative diseases and open up new avenues for therapeutic development.

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Section: Expert Commentarymentioning

confidence: 99%

Network modeling to identify new mechanisms and therapeutic targets for Parkinson’s disease

MacArthur

Ressom

Shah

et al. 2013

Expert Review of Neurotherapeutics

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“…Parkin mediates the proteasome dependent ubiquitylation of PDCD2-1 and increased level of this substrate is found in substantia nigra from ARPD and sporadic PD subjects [46]. Thus, parkin is regulating cellular proliferation by association with several important cell cycle regulatory molecules.…”

Section: Regulation Of Genomic Translation and The Cell Cyclementioning

confidence: 99%

Parkin- An E3 Ubiquitin Ligase with Multiple Substrates

Sandebring¹

2012

J Alzheimers Dis Parkinsonism

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“…The E3 ubiquitin protein ligase Parkin plays a role in the proteasome-mediated turnover of several proteins in vitro [105][106][107][108], some of which accumulate in the brains of AR-JP patients and/or mice carrying a targeted deletion of the Parkin gene, showing that they are authentic Parkin substrates in vivo [109][110][111]. Drosophila lacking Parkin display increased sensitivity to oxidative stress, dopaminergic neuron loss, and severe structural mitochondrial abnormalities in muscle and germline tissues associated with apoptotic muscle degeneration and male sterility [112][113][114].…”

Section: Mitochondrial Function and Dynamics In Parkinson's Diseasementioning

confidence: 99%

Mitochondrial dynamics, cell death and the pathogenesis of Parkinson’s disease

Büeler

2010

Apoptosis

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The structure and function of the mitochondrial network is regulated by mitochondrial biogenesis, fission, fusion, transport and degradation. A well-maintained balance of these processes (mitochondrial dynamics) is essential for neuronal signaling, plasticity and transmitter release. Core proteins of the mitochondrial dynamics machinery play important roles in the regulation of apoptosis, and mutations or abnormal expression of these factors are associated with inherited and age-dependent neurodegenerative disorders. In Parkinson's disease (PD), oxidative stress and mitochondrial dysfunction underlie the development of neuropathology. The recessive Parkinsonism-linked genes PTEN-induced kinase 1 (PINK1) and Parkin maintain mitochondrial integrity by regulating diverse aspects of mitochondrial function, including membrane potential, calcium homeostasis, cristae structure, respiratory activity, and mtDNA integrity. In addition, Parkin is crucial for autophagy-dependent clearance of dysfunctional mitochondria. In the absence of PINK1 or Parkin, cells often develop fragmented mitochondria. Whereas excessive fission may cause apoptosis, coordinated induction of fission and autophagy is believed to facilitate the removal of damaged mitochondria through mitophagy, and has been observed in some types of cells. Compensatory mechanisms may also occur in mice lacking PINK1 that, in contrast to cells and Drosophila, have only mild mitochondrial dysfunction and lack dopaminergic neuron loss. A better understanding of the relationship between the specific changes in mitochondrial dynamics/turnover and cell death will be instrumental to identify potentially neuroprotective pathways steering PINK1-deficient cells towards survival. Such pathways may be manipulated in the future by specific drugs to treat PD and perhaps other neurodegenerative disorders characterized by abnormal mitochondrial function and dynamics.

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Programmed cell death‐2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease

Cited by 31 publications

References 14 publications

Network modeling to identify new mechanisms and therapeutic targets for Parkinson’s disease

Network modeling to identify new mechanisms and therapeutic targets for Parkinson’s disease

Parkin- An E3 Ubiquitin Ligase with Multiple Substrates

Mitochondrial dynamics, cell death and the pathogenesis of Parkinson’s disease

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