Ellen Gerhardt
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Controlling Protein Immobilization over Poly(3-hydroxybutyrate) Microparticles Using Substrate Binding Domain from PHA Depolymerase Open
Biointerface decoration with ligands is a crucial requirement to modulate biodistribution, increase half-life, and provide navigation control for targeted micro- or nanostructured systems. To better control the process of ligand functional…
SUMOylation modulates mitochondrial dynamics in an in vitro rotenone model of Parkinson's disease Open
SUMOylation is a post-translational modification essential for various biological processes. SUMO proteins bind to target substrates in a three-step enzymatic pathway, which is rapidly reversible by the action of specific proteases, known …
View article: α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway
α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway Open
Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we in…
Synphilin-1 as a modulator of aSyn assembly Open
Alpha-synuclein (aSyn) is an intrinsically disordered protein that undergoes phase-separation and is associated with several neurodegenerative conditions. However, the function and the pathological role of aSyn are still elusive. Here, we …
Inhibition of <span>26S</span> proteasome activity by α‐synuclein is mediated by the proteasomal chaperone Rpn14/<span>PAAF1</span> Open
Parkinson's disease (PD) is characterized by aggregation of α‐synuclein (α‐syn) into protein inclusions in degenerating brains. Increasing amounts of aggregated α‐syn species indicate significant perturbation of cellular proteostasis. Alte…
Synphilin-1 as a modulator of aSyn assembly Open
Alpha-synuclein (aSyn) is an intrinsically disordered protein associated with Parkinson’s disease and other synucleinopathies, where it accumulates in pathognomonic protein inclusions in the brain. However, both the physiological function …
View article: miR-101a-3p Impairs Synaptic Plasticity and Contributes to Synucleinopathy
miR-101a-3p Impairs Synaptic Plasticity and Contributes to Synucleinopathy Open
Background: Synucleinopathies are disorders characterized by the abnormal accumulation of α-synuclein (aSyn). Synaptic compromise is observed in synucleinopathies parallel to aSyn aggregation and is accompanied by transcript deregulation. …
Molecular Mechanisms Mediating the Transfer of Disease-Associated Proteins and Effects on Neuronal Activity Open
Background: Various cellular pathways have been implicated in the transfer of disease-related proteins between cells, contributing to disease progression and neurodegeneration. However, the overall effects of protein transfer are still unc…
Ectosomes and exosomes modulate neuronal spontaneous activity Open
Extracellular vesicles (EVs) are important mediators in intercellular communication. However, understanding the biological origin and functional effects of EVs subtypes has been challenging due to the moderate differences in their physical…
Non-SUMOylated alternative spliced isoforms of alpha-synuclein are more aggregation-prone and toxic Open
Background: To date, four alternative splicing isoforms arising from exon skipping have been identified for α-Synuclein (α-Syn), the main constituent of the abnormal protein aggregation in Lewy bodies of Parkinson's disease (PD). In contra…
A water-soluble manganese(II) octanediaoate/phenanthroline complex acts as an antioxidant and attenuates alpha-synuclein toxicity Open
The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds ha…
View article: Rapidly Signal‐enhanced Metabolites for Atomic Scale Monitoring of Living Cells with Magnetic Resonance
Rapidly Signal‐enhanced Metabolites for Atomic Scale Monitoring of Living Cells with Magnetic Resonance Open
Nuclear magnetic resonance (NMR) is widely applied from analytics to biomedicine although it is an inherently insensitive phenomenon. Overcoming sensitivity challenges is key to further broaden the applicability of NMR and, for example, im…
Monitoring the interactions between alpha-synuclein and Tau in vitro and in vivo using bimolecular fluorescence complementation Open
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are characterized by pathological accumulation and aggregation of different amyloidogenic proteins, α-synuclein (aSyn) in PD, and amyloid-β (Aβ) and Tau in AD. Strikingly, few PD and AD…
A Water-Soluble Manganese(II) Octanediaoate/Phenanthroline Complex Acts as an Antioxidant and Attenuates Alpha-Synuclein Toxicity Open
The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds ha…
Monitoring Alpha-Synuclein – Tau Interactions In Vitro and In Vivo Using Bimolecular Fluorescence Complementation Open
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are characterized by pathological accumulation and aggregation of different amyloidogenic proteins, α-synuclein (aSyn) in PD, and amyloid-β (Aβ) and Tau in AD. Strikingly, few PD and AD…
Common molecular mechanisms underlie the transfer of alpha-synuclein, Tau and huntingtin and modulate spontaneous activity in neuronal cells Open
The misfolding and accumulation of disease-related proteins are common hallmarks among several neurodegenerative diseases. Alpha-synuclein (aSyn), Tau and huntingtin (wild-type and mutant, 25QHtt and 103QHtt, respectively) were recently sh…
Ectosomes and exosomes are distinct proteomic entities that modulate spontaneous activity in neuronal cells Open
Summary Extracellular vesicles (EVs) are important mediators in intercellular communication. However, understanding the biological origin and functional effects of EVs subtypes has been challenging due to the moderate differences in their …
View article: Cofilin pathology is a new player on α-synuclein-induced spine impairment in models of hippocampal synucleinopathy
Cofilin pathology is a new player on α-synuclein-induced spine impairment in models of hippocampal synucleinopathy Open
Cognitive dysfunction and dementia are presently recognized as major complications in α-synucleinopathies, namely in Dementia with Lewy Bodies (DLB) and Parkinson’s disease with dementia (PDD). In these disorders, α-Synuclein (αSyn) accumu…
Synucleinopathies: Where we are and where we need to go Open
Synucleinopathies are a group of disorders characterized by the accumulation of inclusions rich in the a‐synuclein (aSyn) protein. This group of disorders includes Parkinson's disease, dementia with Lewy bodies (DLB), multiple systems atro…
Characterization of the activity, aggregation, and toxicity of heterodimers of WT and ALS-associated mutant Sod1 Open
Significance Aggregation of the antioxidant enzyme Sod1 represents common factors of both familial (fALS) and sporadic cases of ALS, a fatal neurodegenerative disease. Although many ALS studies have focused on Sod1 homodimers/homomers, the…
View article: Cytosolic Trapping of a Mitochondrial Heat Shock Protein Is an Early Pathological Event in Synucleinopathies
Cytosolic Trapping of a Mitochondrial Heat Shock Protein Is an Early Pathological Event in Synucleinopathies Open
Alpha-synuclein (aSyn) accumulates in intracellular inclusions in synucleinopathies, but the molecular mechanisms leading to disease are unclear. We identify the 10 kDa heat shock protein (HSP10) as a mediator of aSyn-induced mitochondrial…
LRRK2, alpha-synuclein, and tau: partners in crime or unfortunate bystanders? Open
The identification of genetic forms of Parkinson's disease (PD) has tremendously expanded our understanding of the players and mechanisms involved. Mutations in the genes encoding for alpha-synuclein (aSyn), LRRK2, and tau have been associ…
View article: Nuclear localization and phosphorylation modulate pathological effects of alpha-synuclein
Nuclear localization and phosphorylation modulate pathological effects of alpha-synuclein Open
Alpha-synuclein (aSyn) is a central player in Parkinson’s disease (PD) but the precise molecular mechanisms underlying its pathogenicity remain unclear. It has recently been suggested that nuclear aSyn may modulate gene expression, possibl…
View article: Membrane binding, internalization, and sorting of alpha-synuclein in the cell
Membrane binding, internalization, and sorting of alpha-synuclein in the cell Open
Alpha-synuclein (aSyn) plays a crucial role in Parkinson's disease (PD) and other synucleinopathies, since it misfolds and accumulates in typical proteinaceous inclusions. While the function of aSyn is thought to be related to vesicle bind…
Correction: Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles Open
[This corrects the article DOI: 10.1371/journal.pone.0157852.].
Implications of fALS Mutations on Sod1 Function and Oligomerization in Cell Models Open
Among the familial forms of amyotrophic lateral sclerosis (fALS), 20% are associated with the Cu,Zn-superoxide dismutase (Sod1). fALS is characterized by the accumulation of aggregated proteins and the increase in oxidative stress markers.…
Tau deletion promotes brain insulin resistance Open
The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic p…
Correction: The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease Open
[This corrects the article DOI: 10.1371/journal.pbio.2000374.].