Neuroinflammation leads to neuronal stress responses that contribute to neuronal dysfunction and loss. However, treatments that stabilize neurons and prevent their destruction are still lacking. Here, we identify the histone methyltransferase G9a as a druggable epigenetic regulator of neuronal vulnerability to inflammation. In murine experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS), we found… Read more »
Posts nach Tags: key
Immune signature of multiple sclerosis-associated depression.
Multiple neurobiological pathways have been implicated in the pathobiology of major depressive disorder (MDD). The identification of reliable biological substrates across the entire MDD spectrum, however, is hampered by a vast heterogeneity in the clinical presentation, presumably as a consequence of heterogeneous pathobiology. One way to overcome this limitation could be to explore disease subtypes… Read more »
Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with continuous neuronal loss. Treatment of clinical progression remains challenging due to lack of insights into inflammation-induced neurodegenerative pathways. Here, we show that an imbalance in the neuronal receptor interactome is driving glutamate excitotoxicity in neurons of MS patients and identify the… Read more »
Identifying CNS-colonizing T cells as potential therapeutic targets to prevent progression of multiple sclerosis
MS is a chronic autoimmune disease of the CNS associated with serious physical and cognitive disability. MS manifests most commonly in young adults with a relapsingremitting disease course (RRMS), in which recurrent episodes (relapses) of neurological symptoms are followed by clinical remission. The majority of MS patients develop a progressive form of the disease, in… Read more »
Comorbid depression in medical diseases
Depression is one of the most common comorbidities of many chronic medical diseases including cancer and cardiovascular, metabolic, inflammatory and neurological disorders. Indeed, the prevalence of depression in these patient groups is often substantially higher than in the general population, and depression accounts for a substantial part of the psychosocial burden of these disorders. Many… Read more »
T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis.
Identifying T cell clones associated with human autoimmunity has remained challenging. Intriguingly, many autoimmune diseases, including multiple sclerosis (MS), show strongly diminished activity during pregnancy, providing a unique research paradigm to explore dynamics of immune repertoire changes during active and inactive disease. Here, we characterize immunomodulation at the single-clone level by sequencing the T cell… Read more »
Bassoon proteinopathy drives neurodegeneration in multiple sclerosis.
Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS. Neuronal overexpression… Read more »
Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis
Fatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS. METHODS: Patients with… Read more »
Perceptions on the value of bodily functions in multiple sclerosis.
BACKGROUND: In neurological diseases presenting with a plethora of symptoms, the value of bodily functions for a given patient might be a guide for clinical management. Multiple sclerosis (MS) is paradigmatic in this respect, and little is known about the value of different bodily functions of patients and their physicians‘ perceptions. METHODS: In a multicenter… Read more »
A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial).
OBJECTIVE: To investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated… Read more »
Control conditions for randomised trials of behavioural interventions in psychiatry: a decision framework.
In psychiatry, comparative analyses of therapeutic options and the aggregation of data from clinical trials across different therapeutic approaches play an important role in clinical decision making, treatment guidelines, and health policy. This approach assumes that trials of pharmacological and behavioural therapies generally produce the same level of evidence when properly designed. However, trial design… Read more »
Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy
Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy… Read more »
Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation
Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activityregulated… Read more »
An online programme to reduce depression in patients with multiple sclerosis: a randomised controlled trial.
BACKGROUND: With a lifetime risk for major depressive disorder of up to 50%, depression is a common comorbidity in multiple sclerosis but remains widely underdiagnosed and untreated. We investigated the potential of a fully automated, internet-based, cognitive behavioural therapy programme, Deprexis, to reduce depressive symptoms in patients with multiple sclerosis. METHODS: For this randomised controlled… Read more »
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1) is permeable to Na+ and Ca2+, and excessive accumulation of these ions is associated with axonal degeneration. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After… Read more »
Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis.
The major known genetic risk factors in multiple sclerosis reside in the major histocompatibility complex (MHC) region. Although there is strong evidence implicating MHC class II alleles and CD4(+) T cells in multiple sclerosis pathogenesis, possible contributions from MHC class I genes and CD8(+) T cells are controversial. We have generated humanized mice expressing the… Read more »
Patient education program to enhance decision autonomy in multiple sclerosis relapse management: a randomized-controlled trial.
BACKGROUND: Contrary to strong recommendations for high-dose intravenous corticosteroid treatment for relapses in multiple sclerosis (MS), uncertainty remains about most aspects of relapse management. Oral corticosteroids administered by physicians or patients themselves or no corticosteroids also appear justifiable. OBJECTIVE: To evaluate an education program that aims to involve patients with MS in decisions on relapse… Read more »
TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.
In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this… Read more »
Evidence-based patient information programme in early multiple sclerosis: a randomised controlled trial.
OBJECTIVE: To evaluate the efficacy of an evidence-based patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). BACKGROUND: Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice… Read more »
Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.
BACKGROUND: Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. OBJECTIVE: To investigate the potential of standardized exercise as a therapeutic… Read more »