Treatment with phosphotidylglycerol-based nanoparticles prevents motor deficits induced by proteasome inhibition: implications for Parkinson's disease.
Failure of the ubiquitin-proteasome system to degrade abnormal proteins may underlie the accumulation of alpha-synuclein and dopaminergic neuronal degeneration that occurs in Parkinson's disease. Consequently, a reduction of functional proteasome activity has been implicated in Parkinson's disease. VP025 (Vasogen Inc.) is a preparation of phospholipid nanoparticles incorporating phosphatidylglycerol that has been shown to have neuroprotective effects. We show that VP025 prevents the deficits in motor coordination and dopamine observed in a proteasome inhibitor rat model of PD. Thus, VP025 may have a therapeutic effect on the impairment of dopaminergic-mediated motor activity induced by proteasome inhibition.
Fitzgerald
Patrick
P
Vasogen Ireland Ltd., Dublin, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Mandel
Arkady
A
Bolton
Anthony E
AE
Sullivan
Aideen M
AM
Nolan
Yvonne
Y
D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D007273:Injections, Intramuscular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D013997:Time Factors
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010715:Phosphatidylglycerols; D010743:Phospholipids; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; D004298:Dopamine