OBJECTIVE: To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability. BACKGROUND: Falling due to postural instability is a significant problem in advancing PD, and is minimally impacted by dopaminergic therapy. Anticholinergic medications increase falling in the elderly. Further, CNS cholinergic neuron loss occurs in PD. We hypothesized that acetylcholine augmentation may reduce frequent falling in subjects with PD. METHODS: We enrolled 23 subjects with PD who reported falling or nearly falling more than 2 times per week. In a randomized, placebo-controlled, crossover design, subjects were given 6 weeks of donepezil or placebo with a 3-week washout between phases. The primary outcomes were daily falls and near falls reported on postcards. Secondary outcomes included scores on the Activities of Balance Confidence Scale, Berg Balance Scale, Clinical Global Impression of Change, Folstein Mini-Mental State Examination, and the motor section of the Unified Parkinson's Disease Rating Scale. RESULTS: Fall frequency per day on placebo was 0.25 +/- 0.08 (SEM) compared with 0.13 +/- 0.03 on donepezil (p < 0.05). The frequency of near falls was not significantly different between phases. The secondary outcomes did not differ; however, there was a trend to improvement on the subject-completed Global Impression of Change scale. CONCLUSIONS: Subjects with PD fell approximately half as often during the 6 weeks on donepezil than on placebo. Larger trials of cholinergic augmentation are warranted in subjects with PD with frequent falls. Classification of evidence: This study provides Class II evidence that donepezil (maximum 10 mg per day) significantly reduced the number of falls in patients with PD (0.13 falls/day, SEM = 0.03) than when taking placebo (0.25 falls/day, SEM = 0.08, p = 0.049).

Dementia is a highly prevalent problem causing considerable disability and mortality and exacting great costs to individuals, their families, and society. The 4 most common neurodegenerative disorders that cause dementia-Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and dementia in Parkinson disease-have different underlying etiologies and pathogenetic mechanisms. There is a great need for early diagnostic markers; functional brain imaging may therefore assist in the detection and differential diagnosis of dementia due to neurodegenerative diseases. Functional imaging such as PET allows in vivo imaging of functional brain activity indicating cerebral blood flow and cerebral glucose metabolism, and PET allows imaging of neurotransmitter activity, including that of the cholinergic, dopaminergic, and serotonergic systems. New PET neuroimaging tracers are being developed for detecting pathologic parameters such as amyloid plaque and microglial activity. The development of molecular imaging is important for early diagnosis of dementia, selection of patients for therapies, and evaluation of therapies.

Tyrosine hydroxylase (TH) enzyme is a rate limiting enzyme in dopamine biosynthesis. Missense mutation in both alleles of the TH gene is known to cause dopamine-related phenotypes, including dystonia and infantile Parkinsonism. However, it is not clear if single allele mutation in TH modifies the susceptibility to the adult form of Parkinson disease (PD). We reported a novel deletion of entire TH gene in an adult with PD. The deletion was first identified by copy number variation (CNV) analysis in a genome-wide association study using Illumina Infinium BeadChips. After screening 635 cases and 642 controls, the deletion was found in one PD case but not in any control. The deletion was confirmed by multiple quantitative PCR (qPCR) assays. There is no additional exonic single nucleotide variant in the one copy of TH gene of the patient. The patient has an age-at-onset of 54 years, no evidence for dystonia, and was responsive to L-DOPA. This case supports the importance of the TH gene in PD pathogenesis and raises more attention to rare variants in candidate genes being a risk factor for Parkinson disease. (c) 2010 Wiley-Liss, Inc.

The aim of this study was to investigate the effects of tandospirone on ataxia in various types of spinocerebellar degeneration (SCD). Fifteen milligram per day of tandospirone was administered to 39 patients with SCD (spinocerebellar atrophy (SCA) 1, five patients; SCA2, six patients; Machado-Joseph disease (MJD), 14 patient; SCA6, five patients; multiple system atrophy-cerebellar type (MSA-C), seven patients; and multiple system atrophy-Parkinson type (MSA-P), two patients). All patients were assessed before and 4 weeks after administration of the drug using the international cooperative ataxia rating scale total score (ARS), total length traveled (TLT) of body stabilometry, and a self-rating depression scale. Statistically, ARS showed a significant difference in MJD (p = 0.005) and SCA6 (p = 0.043). TLT also showed a significant difference in MJD (p = 0.002) and SCA6 (p = 0.043). Eight of 39 patients (SCA1, 1/5; SCA2, 0/6; MJD, 4/14; SCA6, 3/5; MSA-C, 0/7; and MSA-P, 0/2) showed more than a five point reduction in ARS, and 13 of 39 patients (SCA1, 0/5; SCA2, 1/6; MJD, 8/14; SCA6, 4/5; MSA-C, 0/7; and MSA-P, 0/2) showed a reduction of TLT. Our data indicate that the effects of tandospirone on ataxia are different between types of SCD. Therefore, tandospirone is useful for cerebellar ataxia in patients with MJD and SCA6.

OBJECTIVES:: To provide evidence regarding the clinical efficacy of cognitive rehabilitation (CR) in early-stage Alzheimer disease (AD). DESIGN:: Single-blind randomized controlled trial comparing CR with relaxation therapy and no treatment. SETTING:: Outpatient, community-based setting. PARTICIPANTS:: Sixty-nine individuals (41 women, 28 men; mean age 77.78 years, standard deviation 6.32, range = 56-89) with a diagnosis of AD or mixed AD and vascular dementia and a Mini-Mental State Examination score of 18 or above, and receiving a stable dose of acetylcholinesterase-inhibiting medication. Forty-four family carers also contributed. INTERVENTION:: Eight weekly individual sessions of CR consisting of personalized interventions to address individually relevant goals supported by components addressing practical aids and strategies, techniques for learning new information, practice in maintaining attention and concentration, and techniques for stress management. MEASUREMENTS:: The primary outcomes were goal performance and satisfaction, assessed using the Canadian Occupational Performance Measure. Questionnaires assessing mood, quality of life and carer strain, and a brief neuropsychological test battery were also administered. A subset of participants underwent functional magnetic resonance imaging (fMRI). RESULTS:: CR produced significant improvement in ratings of goal performance and satisfaction, whereas scores in the other two groups did not change. Behavioral changes in the CR group were supported by fMRI data for a subset of participants. CONCLUSIONS:: The findings support the clinical efficacy of CR in early-stage AD. CR offers a means of assisting people with early-stage AD and their families in managing the effects of the condition.

The molecular motor dynein and its associated regulatory subunit dynactin have been implicated in several neurodegenerative conditions of the basal ganglia, such as Huntington's disease and Perry syndrome, an atypical Parkinson-like disease. This pathogenic role has been largely postulated from the existence of mutations in the dynactin subunit p150(Glued). However, dynactin is also able to act independently of dynein, and there is currently no direct evidence linking dynein to basal ganglia degeneration. To provide such evidence, we used here a mouse strain carrying a point mutation in the dynein heavy chain gene that impairs retrograde axonal transport. These mice exhibited motor and behavioural abnormalities including hindlimb clasping, early muscle weakness, incoordination and hyperactivity. In vivo brain imaging using MRI showed striatal atrophy and lateral ventricle enlargement. In the striatum, altered dopamine signalling, decreased dopamine D1 and D2 receptor binding in PET SCAN and prominent astrocytosis were observed although there was no neuronal loss either in the striatum or substantia nigra. In vitro, dynein mutant striatal neurons displayed strongly impaired neuritic morphology. Altogether, these findings provide a direct genetic evidence for the requirement of dynein for the morphology and function of striatal neurons. Our study supports a role for dynein dysfunction in the pathogenesis of neurodegenerative disorders of the basal ganglia such as Perry syndrome and Huntington's disease.

Rotenone, a mitochondrial complex 1 inhibitor causes oxidative damage via production of reactive oxygen species. We examined the pathophysiology of neuronal and glial cells of the nigro-striatal pathway following unilateral infusion of varying doses of rotenone into the substantia nigra or medial forebrain bundle of adult male Sprague-Dawley rats, sacrificed 14 and 60days post infusion. Immunofluorescence techniques were used to qualitatively and quantitatively assay dopaminergic neurons, their projections, glial cells, synapses and oxidative stress. Rotenone infusion into the substantia nigra at all concentrations caused extensive damage and tissue necrosis, therefore of limited relevance for producing a Parkinson disease model. Infusion of 0.5mug of rotenone targeting the medial forebrain bundle induced oxidative stress in dopaminergic neurons causing ongoing cell stress as defined by an elevation of stress granule and oxidative stress markers. This treatment resulted in the loss of tyrosine hydroxylase immunoreactive cells in the substantia nigra (p</=0.01), and loss of tyrosine hydroxylase immunoreactive nerve fibres and synaptic specialisations in the striatum (p</=0.01). The infusion of 0.5mug rotenone also caused an increase in astrocytes and microglial cells in the substantia nigra in comparison to control (p</=0.01). We examined the time-dependent reduction of tyrosine hydroxylase positive nerve fibres and cell bodies in the striatum and substantia nigra respectively, with a progressive reduction evident 60days post-infusion (p</=0.01, p</=0.05). Dopaminergic axons exposed to low dose rotenone undergo oxidative stress, with a resultant ongoing loss of dopaminergic neurons, providing an animal model relevant to Parkinson disease.

Alzheimer, Parkinson and other neurodegenerative diseases involve a series of brain proteins, referred to as 'amyloidogenic proteins', with exceptional conformational plasticity and a high propensity for self-aggregation. Although the mechanisms by which amyloidogenic proteins kill neural cells are not fully understood, a common feature is the concentration of unstructured amyloidogenic monomers on bidimensional membrane lattices. Membrane-bound monomers undergo a series of lipid-dependent conformational changes, leading to the formation of oligomers of varying toxicity rich in beta-sheet structures (annular pores, amyloid fibrils) or in alpha-helix structures (transmembrane channels). Condensed membrane nano- or microdomains formed by sphingolipids and cholesterol are privileged sites for the binding and oligomerisation of amyloidogenic proteins. By controlling the balance between unstructured monomers and alpha or beta conformers (the chaperone effect), sphingolipids can either inhibit or stimulate the oligomerisation of amyloidogenic proteins. Cholesterol has a dual role: regulation of protein-sphingolipid interactions through a fine tuning of sphingolipid conformation (indirect effect), and facilitation of pore (or channel) formation through direct binding to amyloidogenic proteins. Deciphering this complex network of molecular interactions in the context of age- and disease-related evolution of brain lipid expression will help understanding of how amyloidogenic proteins induce neural toxicity and will stimulate the development of innovative therapies for neurodegenerative diseases.

Tetrahydroberberine (THB) exhibits neuroprotective effects but its targets and underlying mechanisms are largely unknown. Emerging evidence indicates that ATP-sensitive potassium (K(ATP)) channels in the substantia nigra pars compacta (SNc) promote Parkinson disease (PD) pathogenesis, thus blocking K(ATP) channels may protect neurons against neuronal degeneration. In the present study, we tested a hypothesis that THB blocks K(ATP) channels in dopaminergic (DA) neurons acutely dissociated from rat SNc. Using perforated patch-clamp recording in current-clamp mode, the functional K(ATP) channels can be opened by persistent perfusion of rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Bath-application of THB reversibly blocks opened K(ATP) channels in a concentration-dependent manner, which is comparable to a classical K(ATP) channel blocker, Tol. Compared to THB analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP), THB exhibits more profound blockade in K(ATP) channels. In addition, exposure of THB alone to the recorded neuron increases action potential firing, and THB also restores rotenone-induced membrane hyperpolarization in the presence of dopamine D2 receptor antagonist (sulpiride), suggesting that THB exhibits an excitatory effect on SNc DA neurons through the block of K(ATP) channels. Collectively, the blockade of neuronal K(ATP) channels by THB in SNc DA neurons is a novel pharmacological mechanism of THB, which may contribute to its neuroprotective effects in PD.

Objective: The retrieval deficit hypothesis states that the lack of deficit in recognition often observed in patients with Parkinson's disease is because of the low retrieval requirements of the task, given that these patients have retrieval and not encoding deficits. To test this hypothesis we investigated recognition memory by familiarity in Parkinson's patients and in patients with Lewy Bodies disease and Parkinson with dementia. Method: We analyzed to what extent the experimental groups were able to recognize by familiarity in a typical yes/no recognition memory task. The experimental groups were patients with early nondemented Parkinson's disease, advanced nondemented Parkinson's disease, demented Parkinson's patients, and patients with dementia with Lewy Bodies. We compared their performance with a group of young and another group of old healthy participants. The estimation of familiarity was made by analyzing recognition of word targets and distractors consisting of combinations of different letters in comparison with a condition in which targets and distractors were composed of similar letters, even though subjects were unaware of the independent variable. Results: The results indicate that familiarity was used at the same level by controls, patients with early Parkinson's disease and patients with dementia with Lewy Bodies. Although late Parkinson patients also used familiarity, its effect was only marginally significant. Patients with Parkinson's disease and dementia were not capable of using familiarity in recognition memory. Conclusions: Our results support the retrieval deficit hypothesis as Parkinson's patients without dementia show no deficit in a situation in which the retrieval requirements are minimal. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by violent, or potentially violent, movements during REM sleep, corresponding to enacted dreams. During sleep monitoring, there is a partial or total loss of the normal muscle atonia during REM sleep. REM sleep behavior disorder predominantly affects elderly subjects without any other disease (idiopathic RBD, a precursor of Parkinson disease and Lewy body dementia) or suffering from various neurological and neurodegenerative diseases, mainly synucleinopathies. In addition to being a treatable cause of nocturnal injury of the patients or their bed-partners, RBD is a fantastic window into motor and cognitive control during REM sleep. Notably, parkinsonism transiently disappears during RBD. The patient's voice is louder and better articulated than when awake, and movements are rapid (but jerky) suggesting that the deleterious message from the basal ganglia to the primary motor cortex is reduced or bypassed. As we observed culturally-acquired behaviors, retired patients practicing their former work with mastered gestures, as well as sentences pronounced with appropriate prosody, gesturing, fluency, and syntax during the RBD, we suggest that these behaviors are generated by the same cortical areas as during wakefulness. This model also enables the demonstration that REM during REM sleep are coded in the same direction as the arm and hand movements, as if the dreamer were scanning the dream images. This online access to the motor and verbal dream scenario (through the video and audio monitoring), and the physiological measures (via the EEG, eye movements, muscle tone, respiration, heart rate), together with the offline access to the mental content (dream report after the awakening) constitute a triangulation for validating new hypotheses about REM sleep and dreams.

ABSTRACT: OBJECTIVE: To apply a scaled, preference-based measure to the evaluation of health-related quality of life (HRQoL) in Parkinson's disease (PD); to evaluate the relationship between disease-specific rating scales and estimated HRQoL; and to identify predictors of diminished HRQoL. BACKGROUND: Scaled, preference-based measures of HRQoL ("utilities") serve as indices of impact of disease, and can be used to generate quality-adjusted estimates of survival for health-economic evaluations. Evaluation of utilities for PD and their correlation with standard rating scales have been limited. METHODS: Utilities were generated using the Health Utilities Index Mark III (HUI-III) on consecutive patients attending a PD Clinic between October 2003 and June 2006. Disease severity, medical, surgical (subthalamic nucleus deep brain stimulation (STN-DBS)), and demographic information was used as model covariates. Predictors of HUI-III utility scores were evaluated using the Wilxocon rank-sum test and linear regression models. RESULTS: 68 men with a diagnosis of PD and a mean age of 74.0 (SD 7.4) were included in the data analysis. Mean HUI-III utility at first visit was 0.45 (SD 0.33). In multivariable models, UPDRS-II score (r2=0.56, P < 0.001) was highly predictive of HRQoL. UPDRS-III was a weaker, but still significant, predictor of utility scores, even after adjustment for UPDRS-II (P = 0.01). CONCLUSIONS: Reduced self-care in PD reflected by worsening UPDRS-II scores is strongly correlated with reductions in generic HRQoL. HUI-III-based health utilities display convergent validity with the UPDRS-II. These findings highlight the importance of measures of independence as determinants of HRQoL in PD, and will facilitate the utilization of existing UPDRS data into economic analyses of PD therapies.

BACKGROUND AND PURPOSE: It is not known whether individuals with Parkinson disease (PD) can practice movements mentally. Before this question can be addressed, a reliable imagery assessment tool must be established. The recently developed Kinesthetic and Visual Imagery Questionnaire (KVIQ) is valid for non-disabled individuals and individuals with stroke. We have extended this work by examining the test-retest reliability and concurrent validity of the KVIQ in individuals with PD. METHODS: Eleven individuals with mild to moderate PD were assessed, while on medication, by the same examiner at 2 sessions (5-12 days apart). Test-retest reliability was measured using intraclass correlation coefficients (ICCs). To examine concurrent validity, KVIQ scores from the second session were compared with a gold standard, the revised Movement Imagery Questionnaire, using Spearman rank order correlation coefficients. RESULTS: There was no significant difference between total KVIQ scores for the test-retest sessions (P > 0.05). Overall, test-retest reliability of the KVIQ was good (ICC = 0.87), and reliability of the subscale of the KVIQ for indexing visual imagery and kinesthetic imagery was also good (ICC = 0.82 and 0.95, respectively). However, the subscale indexing axial visual imagery showed less reliability (ICC = 0.74), suggesting that individuals with PD were not as reliable when imagining axial visual movements as they were for imagining limb movements. Concurrent validity between the second session KVIQ score and the revised Movement Imagery Questionnaire score (gold standard) was excellent (rho = 0.93). CONCLUSION: Our data support the conclusion that the KVIQ is a reliable and valid test for indexing mental imagery ability in individuals with PD. The KVIQ is easy to administer, and the movements (both real and imagined) required are appropriate for individuals with neuropathology. Our data suggest that the KVIQ is a good choice for clinicians who may wish to index motor imagery ability before implementing imagery as a rehabilitation intervention.

Mitochondrial dysfunction is an early sign of many neurodegenerative diseases. Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy). PINK1 kinase activity is needed for prompt and efficient Parkin recruitment to impaired mitochondria. PD-associated Parkin mutations interfere with the process of mitophagy at distinct steps. Here we show that whole mitochondria are turned over via macroautophagy. Moreover, disease-associated PINK1 mutations also compromise the selective degradation of depolarized mitochondria. This may be due to the decreased physical binding activity of PD-linked PINK1 mutations to Parkin. Thus, PINK1 mutations abrogate autophagy of impaired mitochondria upstream of Parkin. In addition to compromised PINK1 kinase activity, reduced binding of PINK1 to Parkin leads to failure in Parkin mitochondrial translocation, resulting in the accumulation of damaged mitochondria, which may contribute to disease pathogenesis.

The histone-like nucleoid structuring (H-NS) protein plays a fundamental role in DNA condensation and is a key regulator of enterobacterial gene expression in response to changes in osmolarity, pH, and temperature. The protein is capable of high-order self-association via interactions of its oligomerization domain. Using crystallography, we have solved the structure of this complete domain in an oligomerized state. The observed superhelical structure establishes a mechanism for the self-association of H-NS via both an N-terminal antiparallel coiled-coil and a second, hitherto unidentified, helix-turn-helix dimerization interface at the C-terminal end of the oligomerization domain. The helical scaffold suggests the formation of a H-NS:plectonemic DNA nucleoprotein complex that is capable of explaining published biophysical and functional data, and establishes a unifying structural basis for coordinating the DNA packaging and transcription repression functions of H-NS.

Recent advances in deriving induced pluripotent stem (iPS) cells from patients offer new possibilities for biomedical research and clinical applications, as these cells could be used for autologous transplantation. We differentiated iPS cells from patients with Parkinson's disease (PD) into dopaminergic (DA) neurons and show that these DA neurons can be transplanted without signs of neurodegeneration into the adult rodent striatum. The PD patient iPS (PDiPS) cell-derived DA neurons survived at high numbers, showed arborization, and mediated functional effects in an animal model of PD as determined by reduction of amphetamine- and apomorphine-induced rotational asymmetry, but only a few DA neurons projected into the host striatum at 16 wk after transplantation. We next applied FACS for the neural cell adhesion molecule NCAM on differentiated PDiPS cells before transplantation, which resulted in surviving DA neurons with functional effects on amphetamine-induced rotational asymmetry in a 6-OHDA animal model of PD. Morphologically, we found that PDiPS cell-derived non-DA neurons send axons along white matter tracts into specific close and remote gray matter target areas in the adult brain. Such findings establish the transplantation of human PDiPS cell-derived neurons as a long-term in vivo method to analyze potential disease-related changes in a physiological context. Our data also demonstrate proof of principle of survival and functional effects of PDiPS cell-derived DA neurons in an animal model of PD and encourage further development of differentiation protocols to enhance growth and function of implanted PDiPS cell-derived DA neurons in regard to potential therapeutic applications.

Neuronal synchronization in basal ganglia circuits plays a key role in the encoding of movement, procedural memory storage and habit formation. Striatal dopamine (DA) depletion during Parkinsonism causes abnormal synchronization in corticobasal ganglia loops resulting in motor dysfunction. However, the dynamics of the striatal microcircuit underlying abnormal synchronization in Parkinsonism is poorly understood. Here we used targeted whole-cell recordings, calcium imaging allowing the recording from dozens of cells simultaneously and analytical approaches, to describe the striking alterations in network dynamics that the striatal microcircuit undergoes following DA depletion in a rat model of Parkinson disease (PD): In addition to a significant enhancement of basal neuronal activity frequent periods of spontaneous synchronization were observed. Multidimensional reduction techniques of vectorized network dynamics revealed that increased synchronization resulted from a dominant network state that absorbed most spontaneously active cells. Abnormal synchronous activity can be virtually abolished by glutamatergic antagonists, while blockade of GABAergic transmission facilitates the engagement of striatal cell assemblies in the dominant state. Finally, a dopaminergic receptor agonist was capable of uncoupling neurons from the dominant state. Abnormal synchronization and "locking" into a dominant state may represent the basic neuronal mechanism that underlies movement disorders at the microcircuit level.

INTRODUCTION: We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. METHODS: Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. RESULTS: There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P < 0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. CONCLUSION: These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications.

DJ-1 is found to be important in human neurodegenerative diseases and cancers by regulating oxidative damage and apoptosis. DJ-1 is also a regulator of PTEN, a frequently mutated tumor suppressor gene in cancers. In this study, we investigated the expression of DJ-1 and PTEN in normal placentas and gestational trophoblastic disease in relation to apoptotic indices and p53 status. A total of 95 trophoblastic samples were retrieved for immunohistochemical study whereas 79 trophoblastic samples, 3 normal trophoblastic and 2 choriocarcinoma cell lines were collected for quantitative real time reverse transcription polymerase chain reaction detection. There was a significant correlation between DJ-1 and PTEN immunostaining indices in the trophoblastic samples (P=0.013). Significantly higher DJ-1 and PTEN immunoreactivity indices were found in the complete mole (P<0.01) and choricarcinoma (P<0.01) compared with the first trimester placenta. Quantitative real time reverse transcription polymerase chain reaction also detected significantly higher messenger ribonucleic acid expressions of DJ-1 and PTEN in hydatidiform moles (P<0.05) and choriocarcinomas (P<0.05) compared with the first trimester placentas. A significant negative correlation was found between DJ-1 and the apoptosis resistant gene Bcl-2 (P=0.031), whereas a positive correlation was shown between PTEN and wild-type p53 (P=0.019). Significant correlations between PTEN and embryonic stem cell transcription factors, Stat3 and Nanog, were also displayed (P=0.001, 0.015). Our findings showed, for the first time, overexpression of DJ-1 at both transcriptional and protein levels in gestational trophoblastic disease. Overexpressed DJ-1 may play a role in regulating apoptotic activities of trophoblasts in relation to PTEN and p53.