-
Maria Corena-McLeod,
Consuelo Walss-Bass,
Alfredo Oliveros,
Andres Gordillo Villegas,
Carolina Ceballos,
Paul J Linser,
Leslie Van Ekeris,
Cristine Charlesworth, Benjamin Madden,
Kristin Smith,
Elliott Richelson
PLoS ONE 05/2013; 8(5):52147. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A series of recent studies has demonstrated that the molecules involved in regulation of neuronal plasticity are also involved in the mode of action of antidepressants and mood stabilizer drugs. Intracellular calcium signaling, energy metabolism, and neuronal plasticity can be influenced by inducing axonal remodeling and increasing levels of certain synaptic proteins. Because antipsychotic drugs are used as mood stabilizers our studies focused on a newly-marketed antipsychotic drug, paliperidone. We determined changes in rat synaptoneurosomal proteins after chronic treatment with paliperidone, lithium salt, or valproic acid in order to find similarities or differences between the mode of action of paliperidone and these two classical mood stabilizers. We determined differential protein expression profiles in prefrontal cortex (PFC) of male Sprague-Dawley rats (n = 4/group). Synaptoneurosomal-enriched preparations were obtained from PFC after chronic treatment with these three drugs. Proteins were separated by 2D-DIGE and identified by nano-LC-MS/MS. We observed similar protein expression profiles at the synaptoneurosomal level, suggesting that the mode of action for paliperidone is similar to that of lithium and valproic acid. However, the expression profile for paliperidone was more similar to that of lithium. Pathways affected in common by these two drugs included oxidative phosphorylation, electron transport, carbohydrate metabolism, and post-synaptic cytokinesis implicating the effects of these drugs in signaling pathways, energy metabolism, and synaptic plasticity.
Brain Research 10/2008; 1233:8-19. · 2.73 Impact Factor
-
Justus C Dächsel,
Julie P Taylor,
Su San Mok,
Owen A Ross,
Kelly M Hinkle,
Rachel M Bailey,
Jacob H Hines,
Jennifer Szutu, Benjamin Madden,
Leonard Petrucelli,
Matthew J Farrer
[show abstract]
[hide abstract]
ABSTRACT: Pathogenic substitutions in the Lrrk2 protein have been shown to be an important cause of both familial and sporadic parkinsonism. The molecular pathway involved in Lrrk2 dopaminergic neuron degeneration remains elusive. Employing a combination of Lrrk2-mediated protein precipitation and tandem mass spectrometry, we identified 14 potential Lrrk2 binding partners. The majority of these interactions may be subgrouped into three functional cellular pathways: (i) chaperone-mediated response, (ii) proteins associated with the cytoskeleton and trafficking and (iii) phosphorylation and kinase activity. Future investigation of these candidates is now warranted and may help resolve the pathomechanism behind Lrrk2 neurodegeneration.
Parkinsonism & Related Disorders 11/2007; 13(7):382-5. · 3.80 Impact Factor
