Effect of naturally occurring α-synuclein-antibodies on toxic α-synuclein-fragments.

Alpha-synuclein (α-Syn) is a soluble protein primarily expressed in presynaptic terminals in the central nervous system (CNS). Aggregates of fibrillated α-Syn are the major component of Lewy bodies (LB), a pathologic hallmark of idiopathic Parkinson's disease (PD). Recently, naturally occurring autoantibodies against human α-Syn (nAbs α-Syn) were detected in the peripheral blood of PD patients and controls.

Heat shock protein 60: an endogenous inducer of dopaminergic cell death in Parkinson disease.

Background: Increasing evidence suggests that inflammation associated with microglial cell activation in the substantia nigra (SN) of patients with Parkinson disease (PD) is not only a consequence of neuronal degeneration, but may actively sustain dopaminergic (DA) cell loss over time. We aimed to study whether the intracellular chaperone heat shock protein 60 (Hsp60) could serve as a signal of CNS injury for activation of microglial cells.

Methods: Hsp60 mRNA expression in the mesencephalon and the striatum of C57/BL6 mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and the Hsp60/TH mRNA ratios in the SN of PD patients and aged-matched subjects were measured.

The α7 nAChR agonist PNU-282987 reduces inflammation and MPTP-induced nigral dopaminergic cell loss in mice.

Background: Parkinson's disease (PD) is associated with neurodegeneration of dopaminergic neurons and an accompanying neuroinflammatory process in the substantia nigra (SN). The cholinergic anti-inflammatory signalling pathway allows the autonomic nervous system to modulate immunologic stimuli and inflammatory processes. A major component of this pathway is the α7 nicotinic acetylcholine receptor (α7 nACh receptor), which is expressed on immune cells such as microglia.

Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease.

In mammalians, toll-like receptors (TLR) signal-transduction pathways induce the expression of a variety of immune-response genes, including inflammatory cytokines. It is therefore plausible to assume that TLRs are mediators in glial cells triggering the release of cytokines that ultimately kill DA neurons in the substantia nigra in Parkinson disease (PD). Accordingly, recent data indicate that TLR4 is up-regulated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in a mouse model of PD.

Differentially expressed gene profile in the 6-hydroxy-dopamine-induced cell culture model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons of the substantia nigra pars compacta with unknown aetiology. 6-Hydroxydopamine (6-OHDA) treatment of neuronal cells is an established in vivo model for mimicking the effect of oxidative stress found in PD brains. We examined the effects of 6-OHDA treatment on human neuroblastoma cells (SH-SY5Y) and primary mesencephalic cultures.

Association of clusterin gene polymorphisms with late-onset Alzheimer's disease.

Background/aims: Some studies have implicated the role of apolipoprotein J [clusterin (CLU), apoJ] in the pathogenesis of Alzheimer's disease (AD). In this study, we investigated the polymorphisms rs11136000 and rs9331888 within CLU in late-onset sporadic AD (LOAD) patients and nondemented subjects.

Methods: LOAD patients and control subjects were analyzed.

RNA editing modulates the binding of drugs and highly unsaturated fatty acids to the open pore of Kv potassium channels.

The time course of inactivation of voltage-activated potassium (Kv) channels is an important determinant of the firing rate of neurons. In many Kv channels highly unsaturated lipids as arachidonic acid, docosahexaenoic acid and anandamide can induce fast inactivation. We found that these lipids interact with hydrophobic residues lining the inner cavity of the pore.

Health-related quality of life and economic burden in patients with restless legs syndrome.

Restless legs syndrome (RLS) is characterized by a distressing, irresistible need or urge to move the legs. It often co-exists with an uncomfortable, though not usually painful, sensation in the legs. Although clear diagnostic criteria and effective treatment options exist, RLS is generally underdiagnosed and under-treated.

Alpha2-macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer's disease.

Alpha2-macroglobulin (alpha2M) as well as its receptor, the low-density lipoprotein receptor-related (LRP) and the receptor-associated protein (RAP) are involved in the clearance of cerebral A beta. Current evidence suggests that polymorphisms in the genes of alpha2M, LRP and RAP may have functional effects on the proteins. Two independent association samples of 271 AD patients and 280 representative controls were investigated whether the risk for developing AD is altered in carriers of polymorphisms in the alpha2M-gene (Va1000Ile), in the LRP-gene (Ala216Val) and in the RAP-gene (Val311Met).

Caffeic acid phenethyl ester prevents neonatal hypoxic-ischaemic brain injury.

Neonatal hypoxic-ischaemic (HI) brain injury resulting in encephalopathy is a leading cause of morbidity and mortality with no effective treatment. Here we show that caffeic acid phenethyl ester (CAPE), an active component of propolis, administered either before or after an HI insult, significantly prevents HI-induced neonatal rat brain damage in the cortex, hippocampus and thalamus. In addition to blocking HI-induced caspase 3 activation, CAPE also inhibits HI-mediated expression of inducible nitric oxide synthase and caspase 1 in vivo and potently blocks nitric oxide-induced neurotoxicity in vitro.

Systematic assessment of decision models in Parkinson's disease.

Objective: To give an insight into the structural and methodological approaches used in published decision-analytic models evaluating interventions in Parkinson's disease (PD) and to derive recommendations for future comprehensive PD decision models.

Methods: A systematic literature review was performed to identify studies that evaluated PD interventions using mathematical decision models. Using a standardized assessment form, information on the study design, methodological framework, and data sources was extracted from each publication and systematically reported.

Resource utilization and costs of stroke unit care in Germany.

Objectives: Stroke imposes a considerable economic burden on the individual and society. Recently, the concept of an integrated stroke unit has been established in several countries to improve the outcome of patients. This study evaluates the costs of acute care of the different cerebrovascular insults in a stroke unit.

Lack of association between the interleukin-1 alpha (-889) polymorphism and early-onset Parkinson's disease.

An increasing number of studies have shown that an inflammatory process is part of Parkinson's disease (PD) brain pathology. Interleukin-1 (IL-1) is a multifunctional cytokine and is considered to contribute to several inflammatory diseases. Recently, we detected an associated risk in a subgroup of PD patients with a disease onset < 50 years and a C to T transition in the IL-1alpha promoter (-889).

An interleukin-6 promoter variant is not associated with an increased risk for Alzheimer's disease.

Recent studies have implicated interleukin-6 (IL-6) in the pathogenesis of Alzheimer's disease (AD). Neuro-inflammatory processes surrounding the amyloid plaques contribute to the progression of AD-related neurodegeneration. IL-6 is a multifunctional inflammatory cytokine which possibly acts as a mediator in the local immune response in the brain of AD patients.

Dopamine transporter imaging and SPECT in diagnostic work-up of Parkinson's disease: a decision-analytic approach.

As a diagnostic test for patients with suspected Parkinson's disease (PD), single photon emission computed tomography (SPECT) using [(123)I]FP-CIT tracer has better sensitivity but is more expensive than regular clinical examination (CE). Our objective was to evaluate the clinical and economic impacts of different diagnostic strategies involving [(123)I]FP-CIT SPECT. We developed a decision tree model to predict adequate treatment-month equivalents (ATME), costs, and incremental cost-effectiveness ratio (ICER) during a 12-month time horizon in patients with suspected PD referred to a specialized movement disorder outpatient clinic.

Role of dopamine transporter SPECT for the practitioner and the general neurologist.

The accurate clinical diagnosis of parkinsonism may be impeded by atypical presentations and confounding comorbidity. The presence of parkinsonism is misdiagnosed in up to a quarter of cases in general practice. Movement disorder specialists misdiagnose parkinsonian syndromes using histopathological findings as the "gold standard" in up to 10% of cases.

Cabergoline versus levodopa monotherapy: a decision analysis.

We evaluated the incremental cost-effectiveness of cabergoline compared with levodopa monotherapy in patients with early Parkinson's disease (PD) in the German healthcare system. The study design was based on cost-effectiveness analysis using a Markov model with a 10-year time horizon. Model input data was based on a clinical trial "Early Treatment of PD with Cabergoline" as well as on cost data of a German hospital/office-based PD network.

Immunotherapy for Alzheimer's disease.

Recent studies in murine models of Alzheimer's disease (AD) have found that active immunisation with amyloid-beta peptide (Abeta) or passive immunisation with Abeta antibodies can lessen the severity of Abeta-induced neuritic plaque pathology through the activation of microglia. These antibodies can be detected in the serum and CSF. Whether they slow down or speed up the development and progression of AD has not been determined.

Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer's disease.

There is increasing evidence that immune mechanisms are involved in the pathogenesis of Alzheimer's disease (AD). Recently, polymorphisms of the interleukin (IL)-1 and IL-6 genes were found to be associated with late-onset AD. The immunoregulatory IL-10 downregulates synthesis of pro-inflammatory cytokines such as IL-1.

NF-kappaB mediates IL-1beta-induced synthesis/release of alpha2-macroglobulin in a human glial cell line.

Increasingly, inflammatory responses in localized areas of brain parenchyma in response to the extracellular deposition of the Abeta peptides are thought to play a causative role in Alzheimer's disease (AD) progression. Anti-inflammatory agents, in particular non-steroid anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, have been shown to be associated with a delayed onset or slowed rate of disease progression in several epidemiological studies. Activation of glial cells and the subsequent expression of a number of proteins including alpha(2)-macroglobulin (alpha(2)M) are associated with the induction of brain tissue inflammation.