Tim E. Moors
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View article: C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson’s disease human brain neurons
C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson’s disease human brain neurons Open
The abnormal accumulation of alpha-Synuclein (αSyn) within neurons is a hallmark of synucleinopathies, such as Parkinson's disease (PD), and could stem from impaired protein degradation. Genetic, in vitro, and post-mortem studies have sugg…
View article: Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice
Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice Open
Loss-of-function mutations in the GBA1 gene are a prevalent risk factor for Parkinson's disease (PD). Defining features are Lewy bodies that can be rich in α-synuclein (αS), vesicle membranes, and other lipid membranes, coupled with striat…
View article: Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson’s disease phenotypes
Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson’s disease phenotypes Open
Mutations in the α-Synuclein (αS) gene promote αS monomer aggregation that causes neurodegeneration in familial Parkinson’s disease (fPD). However, most mouse models expressing single-mutant αS transgenes develop neuronal aggregates very s…
View article: Defining a Lewy Body: Running Up the Hill of Shifting Definitions and Evolving Concepts
Defining a Lewy Body: Running Up the Hill of Shifting Definitions and Evolving Concepts Open
Lewy bodies (LBs) are pathological hallmarks of Parkinson’s disease and dementia with Lewy bodies, characterized by the accumulation of α-synuclein (αSyn) protein in the brain. While LBs were first described a century ago, their formation …
View article: Increased palmitoylation improves estrogen receptor alpha–dependent hippocampal synaptic deficits in a mouse model of synucleinopathy
Increased palmitoylation improves estrogen receptor alpha–dependent hippocampal synaptic deficits in a mouse model of synucleinopathy Open
Parkinson’s disease (PD) is characterized by conversion of soluble α-synuclein (αS) into intraneuronal aggregates and degeneration of neurons and neuronal processes. Indications that women with early-stage PD display milder neurodegenerati…
View article: Altered TFEB subcellular localization in nigral dopaminergic neurons of subjects with prodromal, sporadic and<i>GBA</i>-related Parkinson’s disease and Dementia with Lewy bodies
Altered TFEB subcellular localization in nigral dopaminergic neurons of subjects with prodromal, sporadic and<i>GBA</i>-related Parkinson’s disease and Dementia with Lewy bodies Open
Transcription factor EB is a master regulator of genes involved in the maintenance of autophagic and lysosomal homeostasis, processes which have been implicated in the pathogenesis of GBA -related and sporadic Parkinson’s disease (PD) and …
View article: Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity
Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity Open
In Parkinson’s disease and other synucleinopathies, the elevation of α-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker of pathology. However, the physiological role for pS129 has remained undefined. Here we use multi…
View article: Wild-type GBA1 increases the α-synuclein tetramer–monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice
Wild-type GBA1 increases the α-synuclein tetramer–monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice Open
Significance The mechanisms responsible for brain α-synuclein (αS) dyshomeostasis, caused by Gaucher’s GBA1 mutations that increase Parkinson’s disease (PD) risk, are largely unknown. We previously showed that abrogating physiological αS t…
View article: The subcellular arrangement of alpha-synuclein proteoforms in the Parkinson’s disease brain as revealed by multicolor STED microscopy
The subcellular arrangement of alpha-synuclein proteoforms in the Parkinson’s disease brain as revealed by multicolor STED microscopy Open
Various post-translationally modified (PTM) proteoforms of alpha-synuclein (aSyn)—including C-terminally truncated (CTT) and Serine 129 phosphorylated (Ser129-p) aSyn—accumulate in Lewy bodies (LBs) in different regions of the Parkinson’s …
View article: Alterations in Sub-Axonal Architecture Between Normal Aging and Parkinson’s Diseased Human Brains Using Label-Free Cryogenic X-ray Nanotomography
Alterations in Sub-Axonal Architecture Between Normal Aging and Parkinson’s Diseased Human Brains Using Label-Free Cryogenic X-ray Nanotomography Open
Gaining insight to pathologically relevant processes in continuous volumes of unstained brain tissue is important for a better understanding of neurological diseases. Many pathological processes in neurodegenerative disorders affect myelin…
View article: More than a synuclein story: Dissecting determinants for alpha-synuclein aggregation and degradation in the Parkinson’s disease brain
More than a synuclein story: Dissecting determinants for alpha-synuclein aggregation and degradation in the Parkinson’s disease brain Open
De ziekte van Parkinson is de snelst groeiende neurologische aandoening ter wereld [1]. In de laatste twintig jaar is het aantal mensen dat lijdt aan de ziekte van Parkinson wereldwijd gestegen tot meer dan 60 miljoen [1]. De kans is aanzi…
View article: Lewy pathology in Parkinson’s disease consists of a crowded organellar, membranous medley
Lewy pathology in Parkinson’s disease consists of a crowded organellar, membranous medley Open
Summary Parkinson’s disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Key neuropathological hallmarks are Lewy bodies and Lewy neurites, which are neuronal inclusions …
View article: Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease
Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease Open
Converging evidence from genetic, pathological and experimental studies have increasingly suggested an important role for autophagy impairment in Parkinson's Disease (PD). Genetic studies have identified mutations in genes encoding for com…