[Research Progress of Pathogenesis and Treatment of Parkinsons Disease].

Parkinson's disease (PD) is the second most common neurodegenerative disease. The most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies in most cases. The most prominent symptom of PD is the impairment of motor behavior due to the loss of dopaminergic neurons and the consequent loss of the dopamine signaling in the basal ganglia.

GBA deficiency promotes SNCA/α-synuclein accumulation through autophagic inhibition by inactivated PPP2A.

Loss-of-function mutations in the gene encoding GBA (glucocerebrosidase, β, acid), the enzyme deficient in the lysosomal storage disorder Gaucher disease, elevate the risk of Parkinson disease (PD), which is characterized by the misprocessing of SNCA/α-synuclein. However, the mechanistic link between GBA deficiency and SNCA accumulation remains poorly understood. In this study, we found that loss of GBA function resulted in increased levels of SNCA via inhibition of the autophagic pathway in SK-N-SH neuroblastoma cells, primary rat cortical neurons, or the rat striatum.

[Overexpression of alpha-synuclein in SH-SY5Y cells partially protected against oxidative stress induced by rotenone].

Both genetic and environmental factors are involved in the pathogenesis of Parkinsonos disease (PD). Epidemiological studies showed that environmental factors shared with the common mechanisms of resulting in alpha-synuclein aggregation by inhibiting complex I of mitochondria and leading to oxidative stress. To investigate the relationship between alpha-synuclein and oxidative stress, we used human dopaminergic SH-SY5Y cells transfected with alpha-synuclein-enhanced green fluorescent protein (EGFP).

The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD.

In the past decades, there have been numerous studies in the gene therapy for Parkinson's disease (PD), especially in delivering genes of enzymes for dopamine (DA) synthesis. Gene therapy in PD appears to be at the brink of the clinical study phase. However, there are many questions that need to be solved before this approach can be contemplated clinically, especially the question about the control of DA production because too much DA could cause toxicity.

Effects of glutamate and MK-801 on the metabolism of dopamine in the striatum of normal and parkinsonian rats.

The direct effects of glutamate and dizocilpine maleate (MK-801, non-competitive N-Methyl-D-aspartate glutamate receptor antagonist) on the metabolism of dopamine were investigated in the striatum of normal and parkinsonian rats. L-dopa, L-glutamic acid and MK-801 were administered in the striatum locally by microdialysis. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were simultaneously sampled by microdialysis.

[Gene therapy of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and GTP cyclohydrolase genes in rat model of Parkinson's disease].

Objective: To detect the expression and function of enzyme genes involved in biosynthetic pathway for dopamine in vitro and assess their effect in rat model of Parkinson's disease.

Methods: Cos7 cells were transfected with separate adeno-associated virus (AAV) expressing tyrosine hydroxylase (TH) gene, aromatic L-amino acid decarboxylase (AADC) gene and GTP cyclohydrolase I (GCH-I) gene. The expression and function of the three genes were detected by methods of immunohistochemistry, in situ hybridization and high performance liquid chromatograph and electrochemical detection (HPLC-ECD).

[Expression and assessment of double genes of tyrosine hydroxylase gene and aromatic L-amino acid decarboxylase gene in vitro].

The characteristic pathological changes of Parkinson s disease (PD) include a severe loss of dopamine neurons in the substantia nigra and a severe decrease in dopamine in the striatum. Since the expression of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) in the biosynthetic pathway for dopamine are low, a promising approach to the gene therapy of PD is to augment the gene expression of the enzymes in the biosynthetic pathway for dopamine. In the present study, human TH and AADC genes were reconstructed into retrovirous vectors pLHCX and pLNCX(2) respectively.