Freezing of gait in Parkinson ’s disease: pathophysiology, risk factors and treatments
ConclusionFOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - April 14, 2020 Category: Neurology Source Type: research
A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson ’s disease potential biomarkers
ConclusionsIn this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson ’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of stat istical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargete...
Source: Translational Neurodegeneration - April 2, 2020 Category: Neurology Source Type: research
Current understanding of metal ions in the pathogenesis of Alzheimer ’s disease
ConclusionThe metal ions imbalance induces A β and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be p otential in ameliorating AD pathologies, which provides new research directions for AD treatment. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - April 2, 2020 Category: Neurology Source Type: research
Effectiveness and safety of opicapone in Parkinson ’s disease patients with motor fluctuations: the OPTIPARK open-label study
ConclusionsOpicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice.Trial registrationRegistered in July 2016 at clinicaltrials.gov (NCT02847442). (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 3, 2020 Category: Neurology Source Type: research
Race modifies default mode connectivity in Alzheimer ’s disease
ConclusionThese findings provide further support that race modifies the AD phenotypes downstream from cerebral amyloid deposition, and identifies key inter-subsystem connections for deep imaging and neuropathologic characterization. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 18, 2020 Category: Neurology Source Type: research
Insights into the pathogenesis of multiple system atrophy: focus on glial cytoplasmic inclusions
AbstractMultiple system atrophy (MSA) is a debilitating and fatal neurodegenerative disorder. The disease severity warrants urgent development of disease-modifying therapy, but the disease pathogenesis is still enigmatic. Neurodegeneration in MSA brains is preceded by the emergence of glial cytoplasmic inclusions (GCIs), which are insoluble α-synuclein accumulations within oligodendrocytes (OLGs). Thus, preventive strategies against GCI formation may suppress disease progression. However, although numerous studies have tried to elucidate the molecular pathogenesis of GCI formation, difficulty remains in understanding the ...
Source: Translational Neurodegeneration - February 16, 2020 Category: Neurology Source Type: research
Reprogrammed astrocytes display higher neurogenic competence, migration ability and cell death resistance than reprogrammed fibroblasts
AbstractThe direct reprogramming of somatic cells into induced neural progenitor cells (iNPCs) has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation. We previously reported that astrocyte-derived induced pluripotent stem cells (iPSCs) have more tendencies for neuronal differentiation than fibroblast-derived iPSCs. However, the differences of neurogenic potential between astrocyte-derived iNPCs (AiNPCs) and iNPCs from non-neural origins, such as fibroblast-derived iNPCs (FiNPCs), and the underlying mechanisms remain unclear. Our results suggested that Ai...
Source: Translational Neurodegeneration - February 7, 2020 Category: Neurology Source Type: research
Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays
ConclusionThe variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols, cohorts and material etc.. An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical hete rogeneity of α-synucleinopathies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 16, 2020 Category: Neurology Source Type: research
Deep brain stimulation for Tourette ’s syndrome
AbstractTourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be ...
Source: Translational Neurodegeneration - January 12, 2020 Category: Neurology Source Type: research
Replacing what ’s lost: a new era of stem cell therapy for Parkinson’s disease
ConclusionWith the maturity of the iPSC technology, cell transplantation appears to be a safe and effective therapy. Grafts in non-human primates survive and remain functional for more than 2 years after transplantation, with no signs of tumorigenesis, indicating safety and efficacy of the treatment. However, immunosuppressants are still required because of the lack of “universal stem cells” that would not evoke an immune response. The results of ongoing and upcoming trials by a g lobal consortium known as GForce-PD would be highly anticipated because the success of these trials would open up possibilities for using...
Source: Translational Neurodegeneration - January 6, 2020 Category: Neurology Source Type: research
δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities
AbstractMammalian asparagine endopeptidase (AEP) is a cysteine protease that cleaves its protein substrates on the C-terminal side of asparagine residues. Converging lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological diseases, including Alzheimer ’s disease, Parkinson’s disease, and frontotemporal dementia. AEP is activated in the aging brain, cleaves amyloid precursor protein (APP) and promotes the production of amyloid-β (Aβ). We renamed AEP to δ-secretase to emphasize its role in APP fragmentation and Aβ production. AEP also cleav es other substrates, such as tau, α-...
Source: Translational Neurodegeneration - January 5, 2020 Category: Neurology Source Type: research
Correction to: Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in
In the original publication of this article [1], the following statement should be added in the Acknowledgement section. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 2, 2020 Category: Neurology Source Type: research
Microbiome changes: an indicator of Parkinson ’s disease?
AbstractParkinson ’s disease is characterized by dopaminergic neuron loss and intracellular inclusions composed mainly of alpha synuclein (α-syn), but the mechanism of pathogenesis is still obscure. In recent years, more attention has been given to the gut as a key player in the initiation and progression of PD pa thology. Several studies characterizing changes in the microbiome, particularly the gut microbiome, have been conducted. Although many studies found a decrease in the bacterial family Prevotellaceae and in butyrate-producing bacterial genera such as Roseburia and Faecalibacteria, and an increase in the genera ...
Source: Translational Neurodegeneration - December 23, 2019 Category: Neurology Source Type: research
Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in
ConclusionsRecent findings from the fields of advanced neuroradiology and neurochemistry provide the promising prospect of demonstrating degenerative brain pathology in patients with MS before atrophy has installed. Although the overall level of evidence on the presented topic is still preliminary, this Review may pave the way for further longitudinal and multimodal studies exploring the relationships between the abovementioned measures, possibly leading to novel insights in early disease mechanisms and therapeutic intervention strategies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 8, 2019 Category: Neurology Source Type: research
Targeting γ-secretase triggers the selective enrichment of oligomeric APP-CTFs in brain extracellular vesicles from Alzheimer cell and mouse models
ConclusionsThis is the first study to demonstrate the presence of oligomeric APP-CTFs in AD mouse models, the levels of which are selectively enriched in endolysosomal compartments including exosomes and amplified by γ-secretase inhibition. Future studies should evaluate the putative contribution of these exosome-associated APP-CTFs in AD onset, progression and spreading. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 4, 2019 Category: Neurology Source Type: research
