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Prof. Dr. Huu Phuc Nguyen

Department of Human Genetics
Medical Faculty
Phone:+49 234 32 23839
Mail: Huu.Nguyen-r7w@rub.de

 

Primary Supervisor – Prof. Dr. Huu Phuc Nguyen

Co-Supervisor – Prof. Dr. Melanie Mark

Aim:  Investigating the interaction of D1R, D2R, A2AR, NMDAR and mGluR5 signaling pathways in Gnal-knockout rats.

Spiny projection neurons (SPNs) are an important cell group in the striatum that express dopamine receptors, either the D1-type receptor (D1R) or the D2-type receptor (D2R). They convey the respective excitatory and inhibitory output signal through a direct (D1R expressing neurons) and indirect (D2R expressing neurons) pathway to the thalamus and further to the cortex, thereby controlling movement. An imbalance between direct and indirect pathway has been proposed as the underlying mechanisms in Parkinson disease (McGregor and Nelson, 2019), Huntington disease (Barry et al., 2018) and dystonia (Simonyan et al., 2017). Besides D1R and D2R, GPCR family members adenosine A2A type receptor (A2AR), N-methyl-D-aspartate receptor (NMDAR) and metabotropic glutamate receptor 5 (mGluR5) are also densely expressed in SPNs. Receptor heterodimerization provides possibilities for signaling crosstalk and direct interaction forming complex signal networks. The networks are generally constructed from a set of interacting proteins. These proteins are often shared between pathways and receive respective positive and negative feedback regulations. We aim to assess the long-term temporal evolution of important proteins in the striatal network after modulation of dopamine signaling.

 

 10 selected publications 

  • Hakim-Eshed V, Boulos A, Cohen-Rosenzweig C, Yu-Taeger L, Ziv T, Kwon YT, Riess O, Nguyen HHP, Ziv NE, Ciechanover A. Site-specific ubiquitination of pathogenic huntingtin attenuates its deleterious effects. Proc Natl Acad Sci U S A.117(31):18661-18669. doi: 10.1073/pnas.2007667117 (2020).

  • Weber JJ, Golla M, Guaitoli G, Wanichawan P, Hayer SN, Hauser S, Krahl AC, Nagel M, Samer S, Aronica E, Carlson CR, Schöls L, Riess O, Gloeckner CJ, Nguyen HP, Hübener-Schmid J. A combinatorial approach to identify calpain cleavage sites in the Machado-Joseph disease protein ataxin-3. Brain. 140(5):1280-1299 (2017).

  • Clemens LE, Weber JJ, Wlodkowski, Yu-Taeger L, Michaud M, Calaminus C, Eckert SH, Gaca J, Weiss A, Magg JCD, Jansson EKH, Eckert GP, Pichler BJ, Bordet T, Pruss RM, Riess O, Nguyen HP. Olesoxime suppresses calpain activation and mutant huntingtin fragmentation in the BACHD rat, Brain 138(Pt 12):3632-53 (2015).

  • Eckmann J*, Clemens LE*, Eckert SH, Hagl S, Yu-Taeger L, Bordet T, Pruss RM, Muller WE, Leuner K, Nguyen HP*, Eckert GP*. Mitochondrial Membrane Fluidity is Consistently Increased in Different Models of Huntington Disease: Restorative Effects of Olesoxime. Mol Neurobiol. 50(1):107-18 (2014). (*equal contribution)

  • Kelp A, Koeppen AH, Petrasch-Parwez E, Calaminus C, Bauer C, Portal E, Yu-Taeger L, Pichler B, Bauer P, Riess O, Nguyen HP. A novel transgenic rat model for spinocerebellar ataxia type 17 recapitulates neuropathological changes and supplies in vivo imaging biomarkers. J Neurosci.  33(21):9068-81 (2013).

  • Hübener J, Weber JJ, Richter C, Honold L, Weiss A, Murad F, Breuer P, Wüllner U, Bellstedt P, Paquet-Durand F, Takano J, Saido TC, Riess O, Nguyen HP. Calpain mediated ataxin-3 cleavage in the molecular pathogenesis of Spinocerebellar Ataxia Type 3 (SCA3). Hum Mol Genet. 22(3):508-18 (2013).

  • Yu-Taeger L, Petrasch-Parwez E, Osmand AP, Redensek A, Metzger S, Clemens LE, Park L, Howland D, Calaminus C, Gu X, Pichler B, Yang XW, Riess O, Nguyen HP. A Novel BACHD Transgenic Rat Exhibits Characteristic Neuropathological Features of Huntington Disease. J Neurosci. 32 (44) :15426-15438 (2012).

  • Hübener J, Vauti F, Funke C, Wolburg H, Ye Y, Schmidt T, Wolburg-Buchholz K, Schmitt I, Gardyan A, Driessen S, Arnold HH, Nguyen HP, Riess O. N-terminal ataxin-3 causes neurological symptoms with inclusions, endoplasmic reticulum stress and ribosomal dislocation. Brain 134 (Pt 7) :1925-42 (2011).

  • Metzger S, Saukko M, Van Che H, Tong L, Puder Y, Riess O, Nguyen HP. Age at onset in Huntington's disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7. Hum Genet. 128 (4) :453-9 (2010).

  • Nguyen HP, Kobbe P, Rahne H, Wörpel T, Jäger B, Stephan M, Pabst R, Holzmann C, Riess O, Korr H, Kántor O, Petrasch-Parwez E, Wetzel R, Osmand A, von Hörsten S. Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington's disease. Hum Mol Genet 15 (21) :3177-94 (2006).