A5019698136- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Neurological disorders and treatments
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Cellular transport and secretion
- Botulinum Toxin and Related Neurological Disorders
- Autism Spectrum Disorder Research
- Mesenchymal stem cell research
- Tryptophan and brain disorders
- Developmental Biology and Gene Regulation
- Neurotransmitter Receptor Influence on Behavior
- Diet and metabolism studies
- Sulfur Compounds in Biology
- Cell Image Analysis Techniques
- Electroconvulsive Therapy Studies
- S100 Proteins and Annexins
- Selenium in Biological Systems
- Transcranial Magnetic Stimulation Studies
Aarhus University
2016-2025
Central Denmark Region
2025
Institute for Disease Modeling
2016
Institute for Biomedicine
2016
GTx (United States)
2012
Lund University
2004-2011
Wallenberg Wood Science Center
2009
University of Florida
2007
Institute of Neurobiology
2005
University of California, Los Angeles
2002-2005
Post-mortem analysis of brains from Parkinson's disease (PD) patients strongly supports microglia activation and adaptive immunity as factors contributing to progression. Such responses may be triggered by alpha-synuclein (alpha-syn), which is known the main constituent aggregated proteins found in Lewy bodies PD patients. To investigate this we used a recombinant viral vector express human alpha-syn rat midbrain at levels that induced neuronal pathology either absence or presence...
Overexpression of human α-synuclein (α-syn) using recombinant adeno-associated viral (rAAV) vectors provides a novel tool to study neurodegenerative processes seen in Parkinson's disease and other synucleinopathies. We used pseudotyped rAAV2/5 vector express wild-type (wt) α-syn, A53T mutated or the green fluorescent protein (GFP) primate ventral midbrain. Twenty-four adult common marmosets (Callithrix jacchus) were followed with regular behavioural tests for 1 year after transduction. α-Syn...
The neuroprotective effect of the glial cell line-derived neurotrophic factor has been extensively studied in various toxic models Parkinson's disease. However, it remains unclear whether this can protect against toxicity induced by aggregation-prone protein α-synuclein. Targeted overexpression human wild-type α-synuclein nigrostriatal system, using adeno-associated viral vectors, causes a progressive degeneration nigral dopamine neurons and development axonal pathology striatum. In present...
The Na(+)/K(+)-ATPase1 alpha subunit 3 (ATP1α(3)) is one of many essential components that maintain the sodium and potassium gradients across plasma membrane in animal cells. Mutations ATP1A3 gene cause rapid-onset dystonia parkinsonism (RDP), a rare movement disorder characterized by sudden onset dystonic spasms slowness movement. To achieve better understanding pathophysiology disease, we used immunohistochemical approaches to describe regional cellular distribution ATP1α(3) adult mouse...
Several studies have suggested an interaction between α-synuclein protein and iron in Parkinson's disease. The presence of together with Lewy bodies, the increase substantia nigra correlation polymorphism several genes implicated metabolism disease, support a role for neurodegeneration. Analysis post mortem brains revealed increased amount insoluble despite unchanged/reduced levels mRNA Interestingly, on basis putative responsive element 5'-UTR, it has been that there is possible...
Human leukocyte antigen-DR induction and lymphocyte infiltrates in the brains of patients with Parkinson disease (PD) presence serum α-synuclein (α-syn)-specific antibodies suggest that peripheral immune system may have an active role progression PD. We designed a vaccination strategy to attempt control these processes mediate protection against rat PD model. Using recombinant adeno-associated viral vector, we unilaterally overexpressed human α-syn substantia nigra induce progressive...
Increasing evidence supports a decisive role for inflammation in the neurodegenerative process of Parkinson's disease (PD). The immune response PD seems to involve, not only microglia, but also other cells infiltrated into brain. Indeed, we observed here infiltration macrophages, specifically CD163+ area neurodegeneration 6-hydroxydopamine (6-OHDA) model. Therefore, investigated therapeutic potential macrophages modulate local microglia brain achieve neuroprotection. To do so, designed...
Abstract Background PD is a multisystem disease where both central and peripheral nervous systems are affected. This systemic involvement also includes the immune response in PD, which implicates not only microglia brain, but cells, such as monocytes; however, this aspect has been understudied. Objectives The purpose of study was to investigate PD‐related changes their responsiveness stimulation, ability release immunomodulatory molecules that might have consequences for progression. Methods...
Abstract Pathology consisting of intracellular aggregates alpha-Synuclein (α-Syn) spread through the nervous system in a variety neurodegenerative disorders including Parkinson’s disease, dementia with Lewy bodies, and multiple atrophy. The discovery structurally distinct α-Syn polymorphs, so-called strains, supports hypothesis where strain-specific structures are templated into formed by native α-Syn. These strains hypothesised to dictate spreading pathology tissue cellular impact...
Alpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinson's disease. The involves not only microglia but also peripheral cells, such as mononuclear phagocytes found blood infiltrated the brain. Understanding involvement essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating early- late-stage disease, defined by disease duration of less or more than five years, respectively, analyze their association clinical...
Abstract The peripheral immune system is important in neurodegenerative diseases, both protecting and inflaming the brain, but underlying mechanisms remain elusive. Alzheimer’s Disease commonly preceded by a prodromal period. Here, we report presence of large Aβ aggregates plasma from patients with mild cognitive impairment ( n = 38). are associated low level Disease-like brain pathology as observed 11 C-PiB PET 18 F-FTP lowered CD18-rich monocytes. We characterize complement receptor 4...
Lineage uncommitted pluripotent stem cells reside in the connective tissue of skeletal muscle. The present study was carried out with (PPSCs) isolated from 6-month old rat Before differentiation, these were vimentin+, CD90+, CD45-, and varied their expression CD34. PPSCs expanded as non-adherent aggregates under similar conditions to those used generate neurospheres embryonic or neural cells. PPSC-derived positive for nestin, an early marker neuronal precursors, expressed two alternative...
Abstract Lewy bodies, which are a pathological hallmark of Parkinson’s disease, contain insoluble polymers alpha‐synuclein (αsyn). Among the different modifications that can promote formation toxic αsyn species, C‐terminal truncation is among most abundant alterations in patients with disease. In vitro , truncated aggregates faster and sub‐stoichiometric amounts aggregation full‐length (αsynFL) induce neuronal toxicity. To address vivo putative stimulation αsyn‐induced pathology by presence...
Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur absence dopaminergic neuron loss PD. We determined early changes rats overexpress human α-synuclein by local injection viral-vectors midbrain. aimed to achieve levels sufficient induce terminal pathology without significant nigral neurons. disruption vivo analyzing motor defects binding a positron...
Alpha-synuclein (a-syn) can aggregate and form toxic oligomers insoluble fibrils which are the main component of Lewy bodies. Intra-neuronal bodies a major pathological characteristic Parkinson's disease (PD). These fibrillar structures act as seeds accelerate aggregation monomeric a-syn. Indeed, recent studies show that injection preformed a-syn (PFF) into rodent brain induce endogenous resulting in neuronal dysfunction eventual cell death. We injected 8 μg murine PFF, or soluble right...
Significance This study shows that the myeloid immune response in isolated rapid-eye-movement sleep behavior disorder (iRBD) patients involves both brain and periphery, these responses are related, supporting a cross-talk between peripheral system. Furthermore, events were correlated with dopaminergic neuronal changes, strongly role for system process associated iRBD putatively Parkinson’s disease. These findings support monocytes as biomarkers potential targets. Future studies should...