title: Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression.
abstract: This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate learning and memory and to the expression of neuronal proteins involved in synaptic plasticity and adult neurogenesis. These properties can be useful in neurological practice to protect and treat neurological disorders, particularly those associated with neurodegeneration and a decline in cognitive functions.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, Raina blv. 19, 1586 Riga, Latvia. vijaklus@latnet.lv, vija.klusa@lu.lv.
authors.forename: Vija
authors.initials: V
authors.lastname: Klusa
authors.forename: Ulrika
authors.initials: U
authors.lastname: Beitnere
authors.forename: Jolanta
authors.initials: J
authors.lastname: Pupure
authors.forename: Sergejs
authors.initials: S
authors.lastname: Isajevs
authors.forename: Juris
authors.initials: J
authors.lastname: Rumaks
authors.forename: Simons
authors.initials: S
authors.lastname: Svirskis
authors.forename: Zane
authors.initials: Z
authors.lastname: Dzirkale
authors.forename: Ivars
authors.initials: I
authors.lastname: Kalvinsh
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007858:Learning / Q000187:drug effects*; D008763:Methylhydrazines / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009443:Neuritis / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D000276:Adjuvants, Immunologic; D008763:Methylhydrazines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C050147:3-(2,2,2-trimethylhydrazine)propionate