Abreviaturas: [DELTA][[psi]m, potencial de membrana mitocondrial; ANT, transportador de nudeotidos de adenosina; EA, enfermedad de Alzheimer; EP enfermedad de Parkinson; EPCR, receptores endoteliales de proteina C; HSP, proteinas de choque termico; IkB, inhibidor kappa B; mPTP
, poro de permeabilidad transicional mitocondrial; NFkB factor nuclear kappa B; PAR-l, receptor-1 activado por proteasa; PCA, proteina C activada; SN, sustancia nigra; TNE factor de necrosis tumoral; VDAC, canal anionico dependiente de voltaje.
The association between MPTP
pollution and parkinsonian symptoms has led investigators to suspect agricultural chemicals to be responsible for the rise in Parkinson's disease among farmers.
Subsequently, symptoms of Parkinson's were induced in monkeys by feeding them MPTP
. This led the medical community to begin thinking of Parkinson's as a disease caused by chemical exposures.
After studies in animals showed that MPTP
interferes with the function of mitochondria within nerve cells, investigators became interested in the possibility that impairment in mitochondrial DNA may be the cause of Parkinson's disease.
It is the first sign of parkinsonism induced by very small doses of MPTP
. In animal models putaminal dopamine levels have been shown to correlate strongly with the degree of akinesia present, as is also the case for human cases of MPTP
intoxication investigated by [.sup.18]fluro-dopa PET scanning (25)(26).
Zhou et al., "Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP
model of Parkinson's disease," Journal of the Neurological Sciences, vol.
AICD: Amyloid precursor protein intracellular domain APP: Amyloid precursor protein BDNF: Brain-derived neurotrophic factor CHOP: CCAAT enhancer-binding protein homologous protein C/N: Carbon to nitrogen ERK: Extracellular-signal-regulated kinase IDE: Insulin-degrading enzyme iNOS: Inducible NO synthase IRE1[alpha]: Inositol-requiring enzyme 1[alpha] JNK: c-Jun N-terminal protein kinase MAPK: Mitogen-activated protein kinase MPTP
: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MP[P.sup.+]: 1-Methyl-4-phenylpyridinium NeuN: Neuronal nuclei NF-[kappa]B: Nuclear factor kappa light chain enhancer of activated B cells NGF: Nerve growth factor PD: Parkinson's disease proNGF: NGF precursor RNS: Reactive nitrogen species TRAF2: Tumor necrosis factor receptor-associated factor 2 v/v: Volume/volume.
They are involved in synaptic transmission and plasticity in progression of LIDs.[sup] Studies on Group I mGluRs, particularly subgroup mGluR5, showed that mGluR5 antagonists are highly efficient in ameliorating motor symptoms and LIDs in animal models.[sup], Enhanced density of postsynaptic metabotropic glutamate 5 (mGlu5) receptor and specific combination with the striatum and posterior putamen observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP
)-lesioned macaque models could contribute to the pathogenesis of LIDs in PD.[sup],, These results formed the basis of several clinical trials evaluating the potential of two mGlu5 receptor negative allosteric modulators (NAMs) — mavoglurant and dipraglurant.
opening is not good because it causes swelling, as water and small chemical molecules flow nonstop into the mitochondria.
One of the main events that trigger mitochondrial dysfunction is mPTP
opening, with subsequent mitochondrial swelling .
Assessment of Mitochondrial Membrane Potential with JC-1 Staining and Mitochondrial Membrane Permeability with MPTP
. The decrease of mitochondrial membrane potential marks the early apoptosis.
Mice in the saline and the MPTP
groups were also lightly immobilized for 60 s without acupuncture and then returned to their cage (Figure 1).