Functional Polymorphisms in PRODH Are Associated with Risk and Protection for Schizophrenia and Fronto-Striatal Structure and Function

Kempf, Lucas; Nicodemus, Kristin K.; Kolachana, Bhaskar; Vakkalanka, Radhakrishna; Verchinski, Beth A.; Egan, Michael; Straub, Richard E.; Mattay, Venkata A.; Callicott, Joseph H.; Weinberger, Daniel R.; Meyer‐Lindenberg, Andreas

doi:10.1371/journal.pgen.1000252

Cited by 100 publications

(81 citation statements)

References 73 publications

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“…In humans, variants of ProDH are associated with schizophrenia (Kempf et al, 2008;Willis et al, 2008) and proline is thought to be a modulator of synaptic transmission (Gogos et al, 1999). Certainly, it is not only plant biologists interested in special properties and metabolism of proline.…”

Section: B Mammalian Biology-connection Of Proline Metabolism To Apomentioning

confidence: 99%

Proline Metabolism and Its Implications for Plant-Environment Interaction

Verslues

Sharma

2010

The Arabidopsis Book

462

347

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Proline has long been known to accumulate in plants experiencing water limitation and this has driven studies of proline as a beneficial solute allowing plants to increase cellular osmolarity during water limitation. Proline metabolism also has roles in redox buffering and energy transfer and is involved in plant pathogen interaction and programmed cell death. Some of these unique roles of proline depend on the properties of proline itself, whereas others depend on the "proline cycle" of coordinated proline synthesis in the chloroplast and cytoplasm with proline catabolism in the mitochondria. The regulatory mechanisms controlling proline metabolism, intercellular and intracellular transport and connections of proline to other metabolic pathways are all important to the in vivo functions of proline metabolism. Connections of proline metabolism to the oxidative pentose phosphate pathway and glutamate-glutamine metabolism are of particular interest. The N-acetyl glutamate pathway can also produce ornithine and, potentially, proline but its role and activity are unclear. Use of model systems such as Arabidopsis thaliana to better understand both these long studied and newly emerging functions of proline can help in the design of nextgeneration experiments testing whether proline metabolism is a promising metabolic engineering target for improving stress resistance of economically important plants.

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Section: B Mammalian Biology-connection Of Proline Metabolism To Apomentioning

confidence: 99%

Proline Metabolism and Its Implications for Plant-Environment Interaction

Verslues

Sharma

2010

The Arabidopsis Book

462

347

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“…Previous studies demonstrated that metabolic abnormalities of schizophrenia were related to glucoregulatory processes and proline metabolism [108][109][110]. A combined UPLC-MS and 1 H NMR-based metabonomics was used to study patients with new-onset neuroleptic-naive schizophrenia before and after a 6-week risperidone monotherapy.…”

Section: Schizophreniamentioning

confidence: 99%

UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry

Zhao

Cheng

Vaziri

et al. 2014

Clinical Biochemistry

118

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a b s t r a c t a r t i c l e i n f oObjectives: Metabonomics is a powerful and promising analytic tool that allows assessment of global lowmolecular-weight metabolites in biological systems. It has a great potential for identifying useful biomarkers for early diagnosis, prognosis and assessment of therapeutic interventions in clinical practice. The aim of this review is to provide a brief summary of the recent advances in UPLC-based metabonomic approach for biomarker discovery in a variety of diseases, and to discuss their significance in clinical chemistry.Design and methods: All the available information on UPLC-based metabonomic applications for discovering biomarkers of diseases were collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Springer, Google Scholar, etc.).Results: Metabonomics has been used in clinical chemistry to identify and evaluate potential biomarkers and therapeutic targets in various diseases affecting the liver (hepatocarcinoma and liver cirrhosis), lung (lung cancer and pneumonia), gastrointestinal tract (colorectal cancer) and urogenital tract (prostate cancer, ovarian cancer and chronic kidney disease), as well as metabolic diseases (diabetes) and neuropsychiatric disorders (Alzheimer's disease and schizophrenia), etc.Conclusions: The information provided highlights the potential value of determination of endogenous lowmolecular-weight metabolites and the advantages and potential drawbacks of the application of UPLC-based metabonomics in clinical setting.

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“…225 Studies have shown that polymorphisms in PRODH are associated with a reduction in bilateral frontal white matter density, decreased striatal volume and increased striatal-frontal functional connectivity, which are all consistent with neuroanatomic findings of schizophrenia. 229,230 Several human association studies have implicated polymorphisms in PRODH with the development of schizophrenia. The first study to implicate PRODH examined a 1.5-Mb region of chromosome 22q11 to address the individual role of the genes in this area and their contribution to the development of schizophrenia.…”

Section: Proline Dehydrogenase (Prodh)mentioning

confidence: 99%