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@ARTICLE{Depboylu:137908,
      author       = {Depboylu, Candan and Rösler, Thomas W and de Andrade,
                      Anderson and Oertel, Wolfgang H and Höglinger, Günter U},
      title        = {{S}ystemically administered neuregulin-1β1 rescues nigral
                      dopaminergic neurons via the {E}rb{B}4 receptor tyrosine
                      kinase in {MPTP} mouse models of {P}arkinson's disease.},
      journal      = {Journal of neurochemistry},
      volume       = {133},
      number       = {4},
      issn         = {0022-3042},
      address      = {Oxford},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2020-04230},
      pages        = {590-597},
      year         = {2015},
      abstract     = {Previously, we demonstrated that systemically injected
                      extracellular domain of neuregulin-1β1 (Nrg1β1), a nerve
                      growth and differentiation factor, passes the blood-brain
                      barrier and rescues dopaminergic neurons of substantia nigra
                      in the 6-hydroxydopamine-mouse model of Parkinson's disease
                      (PD). Here, we studied the effects of peripherally
                      administered Nrg1β1 in another toxin-based mouse model of
                      PD. For this purpose, (i) nigrostriatal pathway injury was
                      induced by treatment of adult wild-type mice with
                      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in acute
                      and subchronic paradigms; and (ii) Nrg1β1 or saline
                      (control) were administered 1 h before each MPTP injection.
                      We found that Nrg1β1 significantly reduced the loss of
                      nigral dopaminergic neurons in both intoxication paradigms
                      (7 days post-injection). However, Nrg1β1 did not reverse
                      MPTP-induced decrease in dopamine levels and dopaminergic
                      fibers in the striatum. We also show that MPTP conversion to
                      its toxic metabolite 1-methyl-4-phenylpyridinium as well as
                      levels of dopamine transporter, mediating intracellular
                      uptake of 1-methyl-4-phenylpyridinium, are unaffected by
                      Nrg1β1. Finally, neuroprotective properties of Nrg1β1 on
                      nigral dopaminergic neurons are specifically mediated by
                      ErbB4 as revealed through the study of ErbB4 knockout mice.
                      In conclusion, systemically administered Nrg1β1 protects
                      midbrain dopaminergic neurons against this PD-related toxic
                      insult. Thus, Nrg1β1 may have a benefit in the treatment of
                      PD patients. Previously, we demonstrated that systemically
                      administered neuregulin-1β1 (Nrg1β1) passes the
                      blood-brain barrier, phosphorylates ErbB4 receptors and
                      elevates dopamine (DA) levels in the nigrostriatal system of
                      healthy mice. Nrg1β1 protects nigral DAergic neurons in the
                      6-hydroxydopamine (6-OHDA) mouse model of Parkinson's
                      disease (PD). Here, we show that Nrg1β1 rescues nigral
                      DAergic neurons also against
                      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
                      cell death. ErbB4 expression is essential for the
                      neuroprotective effect of Nrg1β1 on midbrain DAergic
                      neurons. Nrg1β1 might be beneficial in PD treatment.},
      keywords     = {1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: pharmacology
                      / Animals / Animals, Genetically Modified / Disease Models,
                      Animal / Dopamine Agents: pharmacology / Dopamine Plasma
                      Membrane Transport Proteins: metabolism / Dopaminergic
                      Neurons: drug effects / MPTP Poisoning: chemically induced /
                      MPTP Poisoning: pathology / Male / Mice / Mice, Inbred C57BL
                      / Neuregulin-1: pharmacology / Neuregulin-1: therapeutic use
                      / Neuroprotective Agents: pharmacology / Neuroprotective
                      Agents: therapeutic use / Receptor, ErbB-4: deficiency /
                      Receptor, ErbB-4: genetics / Substantia Nigra: pathology /
                      Time Factors / Dopamine Agents (NLM Chemicals) / Dopamine
                      Plasma Membrane Transport Proteins (NLM Chemicals) /
                      Neuregulin-1 (NLM Chemicals) / Neuroprotective Agents (NLM
                      Chemicals) / neuregulin beta (NLM Chemicals) /
                      1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NLM Chemicals)
                      / Erbb4 protein, mouse (NLM Chemicals) / Receptor, ErbB-4
                      (NLM Chemicals)},
      cin          = {AG Höglinger 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1110002},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25581060},
      doi          = {10.1111/jnc.13026},
      url          = {https://pub.dzne.de/record/137908},
}