Autophagy induction by tetrahydrobiopterin deficiency

Kwak, Sang Su; Suk, Jinkyu; Choi, Ji Hye; Yang, Seungkyung; Kim, Jin Woo; Sohn, Seonghyang; Chung, Jae Hoon; Hong, Yong Hee; Lee, Dong Hwan; Ahn, Jeong Keun; Min, Hyesun; Fu, Yiming; Meadows, Gary G.; Joe, Cheol O.

doi:10.4161/auto.7.11.16627

Cited by 20 publications

(14 citation statements)

References 58 publications

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“…Several reports have shown that lacking biogenic monoamines like dopamine and serotonin-induced growth retardation in knockout mice [49–52]. The same phenomenon is noted in the present study.…”

Section: Discussionsupporting

confidence: 92%

“…In addition, AADC deficiency patients have higher L-Dopa and imbalanced glucose metabolism, which may also influence brain growth and functions [60]. Despite these clinical observations, no morphological or histo-pathological studies in early brain development in animal models have been done for the reduction of brain volume in AADC deficiency [49–52]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

et al. 2013

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Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

et al. 2013

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“…DDC provides dopamine by conversion from dopa, which also can be used for melanin production, such as in butterfly wings (44). PAH supplies tyrosine for melanin production and contributes to melanogenesis (45), and PAH (Enu) mice have inactive TORC1 (46). The role of TOR signaling in melanin pigmentation has also been observed in Drosophila, such that increased TORC1 activity resulted in altered pigmentation (47).…”

Section: Discussionmentioning

confidence: 99%

Functionally conserved effects of rapamycin exposure on zebrafish

Sucularli¹,

Shehwana²,

Kuscu³

et al. 2016

Molecular Medicine Reports

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Abstract. Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase important in cell proliferation, growth and protein translation. Rapamycin, a well-known anti-cancer agent and immunosuppressant drug, inhibits mTOR activity in different taxa including zebrafish. In the present study, the effect of rapamycin exposure on the transcriptome of a zebrafish fibroblast cell line, ZF4, was investigated. Microarray analysis demonstrated that rapamycin treatment modulated a large set of genes with varying functions including protein synthesis, assembly of mitochondrial and proteasomal machinery, cell cycle, metabolism and oxidative phosphorylation in ZF4 cells. A mild however, coordinated reduction in the expression of proteasomal and mitochondrial ribosomal subunits was detected, while the expression of numerous ribosomal subunits increased. Meta-analysis of heterogeneous mouse rapamycin microarray datasets enabled the comparison of zebrafish and mouse pathways modulated by rapamycin, using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway analysis. The analyses demonstrated a high degree of functional conservation between zebrafish and mice in response to rapamycin. In addition, rapamycin treatment resulted in a marked dose-dependent reduction in body size and pigmentation in zebrafish embryos. The present study is the first, to the best of our knowledge, to evaluate the conservation of rapamycin-modulated functional pathways between zebrafish and mice, in addition to the dose-dependent growth curves of zebrafish embryos upon rapamycin exposure.

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“…The administration of BH 4 and neurotransmitter precursors could rescue the growth retardation and high phenylalanine levels, but the level of BH 4 and tyrosine hydroxylase in the brain depends on the method of administration. Furthermore, the tyrosine diet ameliorates the abnormal motor behaviours and enhances mTORC1 activity without affecting dopamine expression in SPR ‐/‐ mice, suggesting that the mTORC1 signalling pathway in the brain is one of the possible targets in understanding the abnormal motor behaviours related to SPD 82,83 …”

Section: Sepiapterin Reductase and Diseasementioning

confidence: 99%

Sepiapterin reductase: Characteristics and role in diseases

Chen

Sun

et al. 2020

J Cellular Molecular Medi

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Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non‐enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research.

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Autophagy induction by tetrahydrobiopterin deficiency

Cited by 20 publications

References 58 publications

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

Functionally conserved effects of rapamycin exposure on zebrafish

Sepiapterin reductase: Characteristics and role in diseases

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