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Article

Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

1
Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga, Latvia
2
Department of Pathology, Faculty of Medicine, University of Latvia, Riga, Latvia
3
Latvian Institute of Organic Synthesis, Riga, Latvia
4
Department of Pathology and Laboratory of Medicine and Neurology, University of California Los Angeles, Los Angeles, CA, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2010, 11(11), 4465-4487; https://doi.org/10.3390/ijms11114465
Received: 20 September 2010 / Revised: 22 October 2010 / Accepted: 27 October 2010 / Published: 9 November 2010
(This article belongs to the Special Issue Neuroprotective Strategies (special issue))
Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease. View Full-Text
Keywords: Parkinson’s disease; 6-OHDA model; neuroimmunological biomarkers; mildronate; small molecule Parkinson’s disease; 6-OHDA model; neuroimmunological biomarkers; mildronate; small molecule
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MDPI and ACS Style

Klusa, V.Z.; Isajevs, S.; Svirina, D.; Pupure, J.; Beitnere, U.; Rumaks, J.; Svirskis, S.; Jansone, B.; Dzirkale, Z.; Muceniece, R.; Kalvinsh, I.; Vinters, H.V. Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease. Int. J. Mol. Sci. 2010, 11, 4465-4487. https://doi.org/10.3390/ijms11114465

AMA Style

Klusa VZ, Isajevs S, Svirina D, Pupure J, Beitnere U, Rumaks J, Svirskis S, Jansone B, Dzirkale Z, Muceniece R, Kalvinsh I, Vinters HV. Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease. International Journal of Molecular Sciences. 2010; 11(11):4465-4487. https://doi.org/10.3390/ijms11114465

Chicago/Turabian Style

Klusa, Vija Z., Sergejs Isajevs, Darja Svirina, Jolanta Pupure, Ulrika Beitnere, Juris Rumaks, Simons Svirskis, Baiba Jansone, Zane Dzirkale, Ruta Muceniece, Ivars Kalvinsh, and Harry V. Vinters 2010. "Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease" International Journal of Molecular Sciences 11, no. 11: 4465-4487. https://doi.org/10.3390/ijms11114465

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