Neurotrophic enhancers as therapy for behavioral deficits in rodent models of Huntington's disease: use of gangliosides, substituted pyrimidines, and mesenchymal stem cells.
The interest in using neurotrophic factors as potential treatments for neurodegenerative disorders, such as Huntington's disease, has grown in the past decade. A major impediment for the clinical utility of neurotrophic factors is their inability to cross the blood-brain barrier in therapeutically significant amounts. Although several novel mechanisms for delivering exogenous neurotrophins to the brain have been developed, most of them involve invasive procedures or present significant risks. One approach to circumventing these problems is using therapeutic agents that can be administered systemically and have the ability to enhance the activity of neurotrophic factors. This review highlights the use of gangliosides, substituted pyrimidines, and mesenchymal stem cells as neurotrophic enhancers that have significant therapeutic potential while avoiding the pitfalls of delivering exogenous neurotrophic factors through the blood-brain barrier. The review focuses on the potential of these neurotrophic enhancers for treating the behavioral deficits in rodent models of Huntington's disease.
Dunbar
Gary L
GL
Central Michigan University, USA.
Sandstrom
Michael I
MI
Rossignol
Julien
J
Lescaudron
Laurent
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000601:surgery; D003511:Cyclohexanols / Q000627:therapeutic use; D004195:Disease Models, Animal; D005732:Gangliosides / Q000627:therapeutic use*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000601:surgery / Q000628:therapy; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D011743:Pyrimidines / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D015854:Up-Regulation
C514429:2-amino-5-(4-chlorophenylethynyl)-4-(4-hydroxycyclohexylamino)pyrimidine; D003511:Cyclohexanols; D005732:Gangliosides; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011743:Pyrimidines