RESUMEN
Parkinson's disease (PD), a progressive neurodegenerative disorder, is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of deposits of aggregated α-synuclein in intracellular inclusions known as Lewy bodies (LB). A highly localized inflammatory response mediated by reactive microglia is prominent in PD brains, but the mechanisms underlying the microglial activation are poorly understood. Recently some lines of evidences have shown that monomeric, or aggregated α-synuclein can activate microglia, the toxic factors released from activated microglia may lead to the cell death of dopaminergic neurons. This review is to summarize the recent progress on the role of α-synuclein induced microglia activation on the PD pathogenesis and progression, and to discuss the possible mechanisms involved.
Asunto(s)
Humanos , Microglía , Patología , Enfermedad de Parkinson , Metabolismo , Patología , alfa-Sinucleína , Química , Metabolismo , FisiologíaRESUMEN
<p><b>OBJECTIVE</b>To examine the protective effect of nicotinamide on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in mouse model and its mechanisms.</p><p><b>METHODS</b>Parkinson's disease was induced by injection of MPTP in adult male C57BL/6 mice, nicotinamide (500 mg/kg,i.p.) was given prior to subacute (30 mg/kg/d × 5 d,i.p.) MPTP administration. Locomotor activities, striatal dopamine levels, lactate dehydrogenase (LDH) and NO synthase (NOS) activities of whole brains and striatum were analyzed at d5 after last MPTP injections.</p><p><b>RESULTS</b>Pretreatment with nicotinamide significantly improved the locomotor activity in the open-field test (P<0.01), but not in the swimming test and grip & climbing test. Nicotinamide administration resulted in sparing striatal dopamine levels from MPTP-induced dopamine depletion. There was no significant difference in LDH and NOS activities in the whole brains among the groups; but the activities in the striatum were drastically elevated after MPTP treatment. Nicotinamide pretreatment markedly inhibited MPTP-induced LDH and NOS activities (P<0.01) and showed no significant difference compared to controls (P>0.05).</p><p><b>CONCLUSION</b>Nicotinamide protects dopaminergic neurons against MPTP-induced neurodegeneration,which suggests that the neuroprotective effects be associated with the inhibition of cell injuries and NOS activities.</p>
Asunto(s)
Animales , Masculino , Ratones , Cuerpo Estriado , Metabolismo , Modelos Animales de Enfermedad , Dopamina , Metabolismo , Ratones Endogámicos C57BL , Actividad Motora , Fisiología , Neuronas , Metabolismo , Niacinamida , Farmacología , Enfermedad de Parkinson , Quimioterapia , MetabolismoRESUMEN
Parkinson's disease (PD) is characterized pathologically by the relatively preferential loss of dopaminergic neurons with resultant depletion of striatal dopamine and presence of Lewy bodies mainly composed by alpha-synuclein (alpha-SYN) in the remaining neurons in the substantia nigra. A lot of evidence suggests that the aggregation of alpha-SYN play an essential role in the pathogenesis of PD and formation of Lewy body. Increasing findings have implicated that some proteins, including parkin, synphilin-1,14-3-3, agrin and tau, interact with alpha-SYN and are involved in the abnormal aggregation of alpha-SYN.
Asunto(s)
Animales , Humanos , Proteínas Portadoras , Metabolismo , Proteínas HSP70 de Choque Térmico , Metabolismo , Cuerpos de Lewy , Metabolismo , Patología , Proteínas del Tejido Nervioso , Metabolismo , Enfermedad de Parkinson , Metabolismo , Dominios y Motivos de Interacción de Proteínas , Sustancia Negra , Patología , alfa-Sinucleína , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the protein profile after treatment of low concentration of N- methyl-N'-nitro-N-nitrosoguanidine (MNNG) in human FL cells.</p><p><b>METHODS</b>After MNNG treatment, whole cellular proteins were separated using two-dimensional gel electrophoresis and visualized by silver staining; the digitized images were analyzed with 2D analysis software. The differentially expressed protein spots were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS).</p><p><b>RESULT</b>More than 60 proteins showed significant changes in MNNG-treated cells compared to control cells (DMSO treatment). There were 18 protein spots detected only after MNNG treatment, while 13 protein spots were detected only in the control cells. Moreover, the levels of another 31 proteins were either increased or decreased in MNNG-treated FL cells. And some of the proteins were identified by MALDI-TOF-MS.</p><p><b>CONCLUSION</b>There are significant alterations of protein profile after MNNG attack.</p>