Compound Formula Rehmannia has been shown to be clinically effective in treating Parkin-son’s disease and levodopa-induced dyskinesia;however, the mechanisms remain unclear. In this study, we established a model of Parkinson’s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson’s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodo-pa-induced dyskinesia in Parkinson’s disease by modulating neurotransmitter signaling in the corpus striatum.

In this study, we established cell models for Parkinson’s disease using rotenone. An RNA interfer-ence vector targeting Parkin-associated endothelin receptor-like receptor (Pael-R) was transfected into the model cells. The results of reverse-transcription polymerase chain reaction and western blot analysis showed that Pael-R expression was decreased after RNA interference compared with the control group (no treatment) and the model group (rotenone treatment), while the rate of apoptosis and survival of dopaminergic cells did not differ signiifcantly between groups, as de-tected by lfow cytometry and an MTT assay. These experimental ifndings indicate that the Pael-R gene has no role in the changes in rotenone-induced Parkinson’s disease model cells.

Previous studies have conifrmed that heat shock protein 90 overexpression can lead to dopami-nergic neuronal death. This study was designed to further investigate what effects are produced by heat shock protein 90 after endurance exercise training. Immunohistochemistry results showed that exercise training signiifcantly inhibited heat shock protein 90 overexpression in the soleus and gastrocnemius in Parkinson’s disease rats, which is a potential therapeutic target for ameliorating skeletal muscle abnormalities in Parkinson’s disease.

Previous studies have shown that baicalin prevented iron accumulation after substantia nigra injury, reduced divalent metal transporter 1 expression, and increased ferroportin 1 expression in the substantia nigra of rotenone-induced Parkinson’s disease rats. In the current study, we investigated the relationship between iron accumulation and transferrin expression in C6 cells, to explore the mechanisms of the inhibitory effect of baicalin on iron accumulation observed in Parkinson’s disease rats. Iron content was detected using inductively coupled plasma-atomic emission spectroscopy. Results showed that iron content decreased 41%after blocking divalent metal transporter 1 and ferroportin 1 proteins. After treatment with ferric ammonium citrate of differing concentrations (10, 50, 100, 400 μg/mL) in C6 glioma cells, cell survival rate and ferroportin 1 expression were negatively correlated with ferric ammonium citrate concentration, but divalent metal transporter 1 expression positively correlated with ferric ammonium citrate concentration. Baicalin or deferoxamine reduced divalent metal transporter 1 expression, but increased ferroportin 1 expression in the 100 μg/mL ferric ammonium citrate-loaded C6 cells. These results indicate that baicalin down-regulated iron concentration, which positively regulat-ed divalent metal transporter 1 expression and negatively regulated ferroportin 1 expression, and decreased iron accumulation in the substantia nigra.

Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 μg/g per day) during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 μg/side per day), striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

X-linked methyl-CpG binding protein 2 mutations can induce symptoms similar to those of Parkin-son’s disease and dopamine metabolism disorders, but the specific role of X-linked methyl-CpG binding protein 2 in the pathogenesis of Parkinson’s disease remains unknown. In the present study, we used 6-hydroxydopamine-induced human neuroblastoma cel (SH-SY5Y cel s) injury as a cel model of Parkinson’s disease. The 6-hydroxydopamine (50 μmol/L) treatment decreased protein levels for both X-linked methyl-CpG binding protein 2 and tyrosine hydroxylase in these cel s, and led to cel death. However, overexpression of X-linked methyl-CpG binding protein 2 was able to ameliorate the effects of 6-hydroxydopamine, it reduced 6-hydroxydopamine-induced apoptosis, and increased the levels of tyrosine hydroxylase in SH-SY5Y cel s. These findings suggesting that X-linked methyl-CpG binding protein 2 may be a potential therapeutic target for the treatment of Parkinson’s disease.

Screening humanized antibodies from a human Fab phage display library is an effective and quick method to obtain beta-amyloid oligomers. Thus, the present study prepared amyloid-beta 42 oli-gomers and constructed a na?ve human Fab phage display library based on blood samples from six healthy people. After three rounds of biopanning in vitro, a human single-domain antibody that spe-cifical y recognized amyloid-beta 42 oligomers was identified. Western blot and enzyme-linked immunosorbent assay demonstrated this antibody bound specifical y to human amyloid-beta 42 te-tramer and nonamer, but not the monomer or high molecular weight oligomers. This study suc-cessful y constructed a human phage display library and screened a single-domain antibody that specifical y recognized amyloid-beta 42 oligomers.

Neuroprotection and neuroregeneration are two of the most promising disease-modifying ther-apies for the incurable and widespread Parkinson’s disease. In Parkinson’s disease, progressive degeneration of nigrostriatal dopaminergic neurons causes debilitating motor symptoms. Neu-rotrophic factors play important regulatory roles in the development, survival and maintenance of speciifc neuronal populations. These factors have the potential to slow down, halt or reverse the loss of nigrostriatal dopaminergic neurons in Parkinson’s disease. Several neurotrophic fac-tors have been investigated in this regard. This review article discusses the neurodevelopmental roles and therapeutic potential of three dopaminergic neurotrophic factors: glial cell line-derived neurotrophic factor, neurturin and growth/differentiation factor 5.

Recently, we have demonstrated the ability of naringin, a well-known flavanone glycoside of grapefruits and citrus fruits, to prevent neurodegeneration in a neurotoxin model of Parkinson’s disease. Intraperitoneal injection of naringin protected the nigrostriatal dopaminergic projection by increasing glial cell line-derived neurotrophic factor expression and decreasing the level of tumor necrosis factor-alpha in dopaminergic neurons and microglia, respectively. These results suggest that naringin can impart to the adult dopaminergic neurons the ability to produce glial cell line-derived neurotrophic factor against Parkinson’s disease with anti-inlfammatory effects. Based on these results, we would like to describe an important perspective on its possibility as a therapeutic agent for Parkinson’s disease.

Both genetic and environmental factors are important in the pathogenesis of Parkinson’s disease. Asα-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson’s dis-ease, genetic aspects ofα-synuclein is widely studied. However, the inlfuence of dietary factors such as quercetin onα-synuclein was rarely studied. Herein we aimed to study the neuropro-tective role of quercetin against various toxins affecting apoptosis, autophagy and aggresome, and the role of quercetin onα-synuclein expression. PC12 cells were pre-treated with quercetin (100, 500, 1,000 μM) and then together with various drugs such as 1-methyl-4-phenylpyridin-ium (MPP+; a free radical generator), 6-hydroxydopamine (6-OHDA; a free radical generator), ammonium chloride (an autophagy inhibitor), and nocodazole (an aggresome inhibitor). Cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltertazolium bromide (MTT) assay. Apoptosis was detected by annexin V-lfuorescein isothiocyanate and propidium iodide through the use of lfuorescence activated cell sorter.α-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of α-synuclein was further studied by knocking outα-synuclein using RNA interference. Cell viability increased at lower concen-trations (100 and 500 μM) of quercetin but decreased at higher concentration (1,000 μM). Quercetin exerted neuroprotective effect against MPP+, ammonium chloride and nocodazole at 100 μM. MPP+ induced apoptosis was decreased by 100 μM quercetin. Quercetin treatment in-creasedα-synuclein expression. However, knocking outα-synuclein exerted no signiifcant effect on cell survival. In conclusion, quercetin is neuroprotective against toxic agentsvia affecting var-ious mechanisms such as apoptosis, autophagy and aggresome. Becauseα-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson’s disease pathogenesis needs further investigation.

Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson’s disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before expo-sure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death pro-cess of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range (5–30 μM) elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Par-kinson’s disease.

The present study aimed to determine whether a polysaccharide obtained fromSpirulina platensis shows protective effects on dopaminergic neurons. A Parkinson’s disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyr-idine (MPTP) in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived fromSpirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopa-mine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were signiifcantly increased in mice pretreated with 800 mg/kg of the poly-saccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased signiifcantly in mice injected with MPTP after pretreatment with the polysaccharide fromSpirulina platensis. By con-trast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental ifndings indicate that the polysaccharide obtained fromSpirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect.

Wistar rats were intragastrical y perfused with Chinese medicines used for tonifying the kidney. These included 0.180 g/mL of Herba Epimedi (Epimedium), Semen Cuscutae (Dodder Seed), or Herba Cistanches (Desertliving Cistanche), 0.04 mg/mL monoamine oxidase-B inhibitor selegiline, or distil ed water for 14 consecutive days to prepare drug-containing serum or blank serum. MES23.5 cells in the logarithmic phase were cultured in media supplemented with 15%drug-containing serum for 24 hours, fol owed by incubation in culture solution containing 100μmol/L H2O2 for 3 hours. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow tometry results showed that al drug-containing serums improved the survival rate of H 2 O 2-injured MES23.5 cells, inhibited pro-apoptotic FasL and caspase-3 expression, promoted anti-apoptotic Bcl-2 expression. However, drug-containing serums had little influence on Fas expression in H 2 O 2-injured MES23.5 cells. Enzyme-linked immunosorbent assay results showed that serum containing Herba Cistanches or Herba Epimedi increased the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cellline-derived neurotrophic factor in injured MES23.5 cells;serum containing Semen Cuscutae only increased brain-derived neurotrophic factor expres-sion; while expression of the above neurotrophic factors remained the same in cells treated with serum containing selegiline. These findings indicate that Chinese medicines used to tonify the kid-ney can protect nerve cells by regulating the expression of apoptosis-related factors and neuro-trophic factors in MES23.5 cells.

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson’s disease during the last 25 years. Besides improving motor symptoms and long-term motor com-plications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues,i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. Al these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases and discusses strategies to modify mitochondrial dysfunction that may be attractive thera-peutic interventions for the treatment of various neurodegenerative diseases.

Subthalamic nucleus deep brain stimulation has become a standard neurosurgical therapy for ad-vanced Parkinson’s disease. Subthalamic nucleus deep brain stimulation can dramatical y improve the motor symptoms of careful y selected patients with this disease. Surprisingly, some specific dimensions of quality of life,“psychological”aspects and social adjustment do not always improve, and they could sometimes be even worse. Patients and their families should ful y understand that subthalamic nucleus deep brain stimulation can alter the motor status and time is needed to readapt to their new postoperative state and lifestyles. This paper reviews the literatures regarding effects of bilateral subthalamic nucleus deep brain stimulation on social adjustment, quality of life and coping strategies in patients with Parkinson’s disease. The findings may help to understand the psychoso-cial maladjustment and poor improvement in quality of life in some Parkinson’s disease patients.

Recent clinical research has demonstrated that berry fruits can prevent age-related neurodegen-erative diseases and improve motor and cognitive functions. The berry fruits are also capable of modulating signaling pathways involved in inflammation, cell survival, neurotransmission and enhancing neuroplasticity. The neuroprotective effects of berry fruits on neurodegenerative diseases are related to phytochemicals such as anthocyanin, caffeic acid, catechin, quercetin, kae-mpferol and tannin. In this review, we made an attempt to clearly describe the beneifcial effects of various types of berries as promising neuroprotective agents.