PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes

Choi, Insup; Choi, Dong Joo; Yang, Haijun; Woo, Joo Hong; Chang, Mi Yoon; Kim, Joo Yeon; Sun, Woong; Park, Sang Myun; Jou, Ilo; Lee, Sang Hoon; Joe, Eun Hye

doi:10.1186/s13041-016-0186-6

Cited by 45 publications

(44 citation statements)

References 70 publications

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“…Accumulating evidences have revealed that functional changes in glial cells due to aging and/or genetic mutation affect onset and progression of neurodegenerative diseases (Graeber & Streit, 2010). We and others have reported that mutation of Parkinson's disease genes such as DJ-1, PINK1, LRRK2, and so on, altered several functions of astrocytes and microglia including neuroprotection, inflammation, migration, proliferation, metabolism, and so on, (Choi et al, 2013;Choi et al, 2015;Choi et al, 2016;Kim et al, 2012;Kim et al, 2013;Mullett, Di Maio, Greenamyre, & Hinkle, 2013;Waak et al, 2009). The results in this study also showed that defects in astrocyte function may be related to Parkinson's disease: DJ-1 deficiency induced defects in astrocyte function in the damaged brain, including defective morphological changes and growth factor production.…”

Section: Discussionmentioning

confidence: 99%

AParkinson's disease gene, DJ‐1, repairs brain injury through Sox9 stabilization and astrogliosis

Choi

Eun

Kim

et al. 2017

Glia

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Defects in repair of damaged brain accumulate injury and contribute to slow-developing neurodegeneration. Here, we report that a deficiency of DJ-1, a Parkinson's disease (PD) gene, delays repair of brain injury due to destabilization of Sox9, a positive regulator of astrogliosis. Stereotaxic injection of ATP into the brain striatum produces similar size of acute injury in wild-type and DJ-1-knockout (KO) mice. However, recovery of the injury is delayed in KO mice, which is confirmed by 9.4T magnetic resonance imaging and tyrosine hydroxylase immunostaining. DJ-1 regulates neurite outgrowth from damaged neurons in a non-cell autonomous manner. In DJ-1 KO brains and astrocytes, Sox9 protein levels are decreased due to enhanced ubiquitination, resulting in defects in astrogliosis and glial cell-derived neurotrophic factor/ brain-derived neurotrophic factor expression in injured brain and astrocytes. These results indicate that DJ-1 deficiency causes defects in astrocyte-mediated repair of brain damage, which may contribute to the development of PD.

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Section: Discussionmentioning

confidence: 99%

AParkinson's disease gene, DJ‐1, repairs brain injury through Sox9 stabilization and astrogliosis

Choi

Eun

Kim

et al. 2017

Glia

Self Cite

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“… When PARK genes are expressed . Data from published papers were normalized to peak expression and then plotted in order to provide a gross comparison of the timing of expression of PARK genes(Beccano‐Kelly et al, ; Bjorkblom et al, ; Choi et al, ; Giesert et al, ; Kuhn, Zhu, Lubbert, & Stichel, ; Petersen et al, ; Wang et al, ; Westerlund et al, )…”

Section: Three Park Gene Groups In Space and Timementioning

confidence: 99%

Are we listening to everything the PARK genes are telling us?

Benson

Huntley

2019

J of Comparative Neurology

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The cardinal motor symptoms that define Parkinson's disease (PD) clinically have been recognized for over 200 years. That these symptoms arise following the loss of dopamine neurons in the substantia nigra has been known for the last 50. These long-established facts have fueled a broadly held expectation that degenerating dopaminergic neurons alone hold the key to understanding and curing PD. This prevalent expectation is at odds with the observation that many nonmotor symptoms, including depression and cognitive inflexibility among others, can appear years earlier than the overt dopaminergic neuron degeneration that drives motor abnormalities and are not improved by levodopa treatment. Thus, preserving or rescuing dopamine neuron health and function is of paramount importance, but this alone fails to capture the underlying neurobiology of earlier-appearing nonmotor symptoms. Insight into the complete landscape of disease-related abnormalities and the context in which they arise can be gleaned from a more comprehensive consideration of the PARK genes that are known to cause PD. Here, we make the case that a full incorporation of research showing when and where PARK genes are expressed as well as the impact of gene mutation on function throughout life, in tandem with research studying how dopaminergic neuron degeneration begins, is essential for a full understanding of the multi-dimensional etiology of PD. A broad view may also reveal something about long-term adjustments cells and systems make in response to gene mutation and help to identify mechanisms conferring the resilience or susceptibility of some cells and systems over others. K E Y W O R D Scritical periods, development, nonmotor symptoms, PARK genes, Parkinson's disease, protein degradation, protein trafficking

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“…Mitophagy precedes mitochondrial biosynthesis and OXPHOS activation and is requisite for differentiation of C2C12 skeletal muscle myoblasts [31]. PINK1 increases during brain development, playing an essential role in neural stem cell differentiation [32]. PINK1 also participates in clearing mitochondria during fibroblast reprogramming, a necessary step for generation of stable iPSCs that do not spontaneously differentiate [33].…”

Section: Mitochondrial Metabolism Provides Fuel For Lifementioning

confidence: 99%

Eat, breathe, ROS: controlling stem cell fate through metabolism

Kubli

Sussman

2017

Expert Review of Cardiovascular Therapy

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Introduction Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

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PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes

Abstract: Background: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown.

Cited by 45 publications

References 70 publications

AParkinson's disease gene, DJ‐1, repairs brain injury through Sox9 stabilization and astrogliosis

AParkinson's disease gene, DJ‐1, repairs brain injury through Sox9 stabilization and astrogliosis

Are we listening to everything the PARK genes are telling us?

Eat, breathe, ROS: controlling stem cell fate through metabolism

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