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Generation of neurons from patient fibroblasts using a combination of developmentally defined transcription factors has great potential in disease modelling, as well as ultimately for use in regeneration and repair. However, generation of physiologically mature neurons in vitro remains problematic. Here we demonstrate the cell-cycle-dependent phosphorylation of a key reprogramming transcription fa

IMPORTANCE: Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood.OBJECTIVE: To define the sleep and circadian phenotype of patients with early-stage Parkinson disease.DESIGN, SETTING, AND PARTICIPANTS: Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at

Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson's disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. It is now recognized that cognitive dysfunction occurs not onl

BACKGROUND: Poor quality of life (QoL) is a feature of people with Parkinson's disease (PD) who develop dementia. The relationship between mild cognitive impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the impact of varying severities of cognitive impairment on QoL in a cohort of non-demented patients with early PD.METHOD: Patients with newly diagnosed PD (n = 219) and

The characteristic and selective degeneration of a unique population of cells-the nigrostriatal dopamine (DA) neurons-that occurs in Parkinson's disease (PD) has made the condition an iconic target for cell replacement therapies. Indeed, transplantation of fetal ventral mesencephalic cells into the DA-deficient striatum was first trialled nearly 30 years ago, at a time when other treatments for th

Filaments made of α-synuclein form the characteristic Lewy pathology in Parkinson and other diseases. The formation of α-synuclein filaments can be reproduced in vitro by incubation of recombinant protein, but the filament growth is very slow and highly variable and so unsuitable for fast high throughput anti-aggregation drug screening. To overcome this obstacle we have investigated whether the pr

The role of glial cells in the pathogenesis of many neurodegenerative conditions of the central nervous system (CNS) is now well established (as is discussed in other reviews in this special issue of Frontiers in Neuropharmacology). What is less clear is whether there are changes in these same cells in terms of their behavior and function in response to invasive experimental therapeutic interventi

We evaluated the association between mild cognitive impairment (MCI) subtypes and quality of life (QoL) in 219 newly diagnosed Parkinson's disease (PD) patients without dementia. Participants completed neuropsychological tests of attention, executive function, visuospatial function, memory, and language, and reported QoL using the Parkinson's Disease Questionnaire. Impairments were most common in

BACKGROUND: Dopaminergic drugs remain the mainstay of Parkinson's disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibiti

BACKGROUND: Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin,

Understanding uptake of nanomaterials by cells and their use for intracellular sensing is important for studying their interaction and toxicology as well as for obtaining new biological insight. Here, we investigate cellular uptake and intracellular dynamics of gold nanoparticles and demonstrate their use in reporting chemical information from the endocytotic pathway and cytoplasm. The intracellul

OBJECTIVE: To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.METHODS: Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Con

Impulsivity is common in Parkinson's disease even in the absence of impulse control disorders. It is likely to be multifactorial, including a dopaminergic 'overdose' and structural changes in the frontostriatal circuits for motor control. In addition, we proposed that changes in serotonergic projections to the forebrain also contribute to response inhibition in Parkinson's disease, based on precli

BACKGROUND: Current clinical assessments of motor function in Huntington's Disease (HD) rely on subjective ratings such as the Unified Huntington's Disease Rating scale (UHDRS). The ability to track disease progression using simple, objective, inexpensive, and robust measures would be beneficial.METHODS: One objective measure of motor performance is hand-tapping. Over the last 14 years we have rou

The 6-hydroxydopamine (6-OHDA) neurotoxic lesion of the midbrain dopamine (DA) system is one of the most widely used techniques for modelling Parkinson's disease in rodents. The majority of studies using this approach, however, largely limit their analysis to lesioning acutely, and looking at behavioural deficits and the number of surviving tyrosine hydroxylase (TH)-stained cells in the midbrain.

Parkinson's disease dementia (PDD) has become an increasing area of research as treatments for the motor features of Parkinson's disease (PD) have improved and the population of patients with PD grows and ages. If predictors could be used to identify a sub-population of patients at risk of developing an early PDD then research into its neuropathological basis and treatment could be more effectivel

Nonmotor symptoms (NMS) are common in patients with established Parkinson's disease (PD) and have a major impact upon quality of life. We investigated the significance of NMS in relation to health-related quality of life (HRQoL) in patients with newly diagnosed PD. Patients and healthy controls were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation

Finding new therapies for Parkinson's disease (PD) is a slow process. We assembled an international committee of experts to examine drugs potentially suitable for repurposing to modify PD progression. This committee evaluated multiple drugs currently used, or being developed, in other therapeutic areas, as well as considering several natural, non-pharmaceutical compounds. The committee prioritized

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical