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Parkinson Disease: HELP
Articles by Wouter Peelaerts
Based on 4 articles published since 2008
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Between 2008 and 2019, W. Peelaerts wrote the following 4 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. 2018

Quansah, Emmanuel / Peelaerts, Wouter / Langston, J William / Simon, David K / Colca, Jerry / Brundin, Patrik. ·Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 333 Bostwick Ave, Michigan, 49503, USA. · KU Leuven, Laboratory for Gene Therapy and Neurobiology, 3000, Leuven, Belgium. · Stanford Udall Center, Department of Pathology, Stanford University, Palo Alto, CA, USA. · Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Metabolic Solutions Development Company, Kalamazoo, MI, 49007, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 333 Bostwick Ave, Michigan, 49503, USA. patrik.brundin@vai.org. ·Mol Neurodegener · Pubmed #29793507.

ABSTRACT: Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson's disease. Failure of cellular energy metabolism has long been implicated in sporadic Parkinson's disease and recent research on rare inherited forms of Parkinson's disease have added further weight to the importance of energy metabolism in the disease pathogenesis. There exists a new class of anti-diabetic insulin sensitizers in development that inhibit the mitochondrial pyruvate carrier (MPC), a protein which mediates the import of pyruvate across the inner membrane of mitochondria. Pharmacological inhibition of the MPC was recently found to be strongly neuroprotective in multiple neurotoxin-based and genetic models of neurodegeneration which are relevant to Parkinson's disease. In this review, we summarize the neuroprotective effects of MPC inhibition and discuss the potential putative underlying mechanisms. These mechanisms involve augmentation of autophagy via attenuation of the activity of the mammalian target of rapamycin (mTOR) in neurons, as well as the inhibition of neuroinflammation, which is at least partly mediated by direct inhibition of MPC in glia cells. We conclude that MPC is a novel and potentially powerful therapeutic target that warrants further study in attempts to slow Parkinson's disease progression.

2 Review ɑ-Synuclein strains and seeding in Parkinson's disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences. 2018

Peelaerts, W / Bousset, L / Baekelandt, V / Melki, R. ·Laboratory for Neurobiology and Gene Therapy, KU Leuven, 3000, Leuven, Belgium. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, 49503, USA. · Paris-Saclay Institute of Neuroscience, CNRS, 91190, Gif-sur-Yvette, France. · Laboratory for Neurobiology and Gene Therapy, KU Leuven, 3000, Leuven, Belgium. veerle.baekelandt@kuleuven.be. ·Cell Tissue Res · Pubmed #29704213.

ABSTRACT: Several age-related neurodegenerative disorders are characterized by the deposition of aberrantly folded endogenous proteins. These proteins have prion-like propagation and amplification properties but so far appear nontransmissible between individuals. Because of the features they share with the prion protein, PrP, the characteristics of pathogenic protein aggregates in several progressive brain disorders, including different types of Lewy body diseases (LBDs), such as Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), have been actively investigated. Even though the pleomorphic nature of these syndromes might suggest different underlying causes, ɑ-synuclein (ɑSyn) appears to play an important role in this heterogeneous group of diseases (the synucleinopathies). An attractive hypothesis is that different types of ɑSyn protein assemblies have a unique and causative role in distinct synucleinopathies. We will discuss the recent research progress on ɑSyn assemblies involved in PD, MSA and DLB; their behavior as strains; current spreading hypotheses; their ability to seed centrally and peripherally; and their implication for disease pathogenesis.

3 Review ɑ-Synuclein strains and the variable pathologies of synucleinopathies. 2016

Peelaerts, Wouter / Baekelandt, Veerle. ·Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. · Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. Veerle.Baekelandt@med.kuleuven.be. ·J Neurochem · Pubmed #26924014.

ABSTRACT: Several decades ago, a mysterious transmissible agent was found responsible for a group of progressive and lethal encephalopathies affecting the nervous system of both animals and humans. This infectious agent showed a strain-encoded manner of inheritance even though it lacked nucleic acids. The identification of infectious proteins resolved this apparent conundrum. Misfolded infectious protein particles, or prions, were found to exist as conformational isomers with a unique fingerprint that can be faithfully passaged to next generations. Protein-based strain-encoded inheritance is characterized by strain-specific infectivity and symptomatology. It is found in diverse organisms, such as yeast, fungi, and mammals. Now, this concept is revisited to examine the pathological role of amyloid proteins involved in neurodegenerative diseases where it might underlie certain types of dementia and motor-related neurodegenerative disorders. Given the discovery of the SNCA gene and the identification of its gene product, ɑ-synuclein (ɑ-SYN), as the main histopathological component of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, the scientific community was left puzzled by the fact that a single protein appeared to be involved in different diseases with diverging clinical phenotypes. Recent studies are now indicating that ɑ-SYN may act in a way similar to prions and that ɑ-SYN misfolded structural variants may behave as strains with distinct biochemical and functional properties inducing specific phenotypic traits, which might finally provide an explanation for the clinical heterogeneity observed between Parkinson's disease, MSA, and dementia with Lewy bodies patients. These crucial new findings may pave the way for unexplored therapeutic avenues and identification of new potential biomarkers. Parkinson's disease and other synucleinopathies share ɑ-synuclein deposits as a common histopathological hallmark. New and ongoing developments are now showing that variations in the aggregation process and the formation of ɑ-synuclein strains may be paralleled by the development of distinct synucleinopathies. Here, we review the recent developments and the role of strains in synucleinopathies. This article is part of a special issue on Parkinson disease.

4 Article α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. 2015

Peelaerts, W / Bousset, L / Van der Perren, A / Moskalyuk, A / Pulizzi, R / Giugliano, M / Van den Haute, C / Melki, R / Baekelandt, V. ·KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium. · Paris-Saclay Institute of Neuroscience, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France. · Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium. · 1] Theoretical Neurobiology &Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium [2] Department of Computer Science, University of Sheffield, S1 4DP Sheffield, UK [3] Brain Mind Institute, Swiss Federal Institute of Technology of Lausanne, 1015 Lausanne, Switzerland [4] Neuro-Electronics Research Flanders (NERF), 3001 Leuven, Belgium. · 1] KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, 3000 Leuven, Belgium [2] KU Leuven, Leuven Viral Vector Core, 3000 Leuven, Belgium. ·Nature · Pubmed #26061766.

ABSTRACT: Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.