Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration.

Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration. Neurobiol Dis. 2019 Jul 24;:104543 Authors: Yeboah F, Kim TE, Bill A, Dettmer U Abstract α-Synuclein (αS) and tau have a lot in common. Dyshomeostasis and aggregation of both proteins is central in the pathogenesis of neurodegenerative diseases: Parkinson's disease, dementia with Lewy bodies, multi-system atrophy and other 'synucleinopathies' in the case of αS; Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy and other 'tauopathies' in the case of tau. The aggregated states of αS and tau are found to be (hyper)phosphorylated, but the relevance of the phosphorylation in health or disease is not well understood. Both tau and αS are typically characterized as 'intrinsically disordered' proteins, while both engage in transient interactions with cellular components, thereby undergoing structural changes and context-specific folding. αS transiently binds to (synaptic) vesicles forming a membrane-induced amphipathic helix; tau transiently interacts with MTs forming an 'extended structure'. The regulation and exact nature of the interactions are not fully understood. Here we review recent and previous insights into the dynamic, transient nature of αS and tau with regard to the mode of interaction with their targets, the dwell-time while bound, and...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research

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Publication date: Available online 24 May 2019Source: Brain StimulationAuthor(s): Alberto Benussi, Valentina Dell’Era, Valentina Cantoni, Rosanna Turrone, Andrea Pilotto, Antonella Alberici, Maria Sofia Cotelli, Cristina Rizzetti, Alessandro Padovani, Barbara BorroniAbstractObjectiveTo determine whether motor cortex inhibition by stimulation over the cerebellum with a figure-of eight coil (MISC8) may be reduced in patients with Progressive Supranuclear Palsy (PSP).MethodsPaired pulse TMS was used to evaluate MISC8, in patients with different forms of parkinsonism and dementia. The primary outcome measures were sensit...
Source: Brain Stimulation - Category: Neurology Source Type: research
Grand Total EEG Score Can Differentiate Parkinson's Disease From Parkinson-Related Disorders Ela Austria Barcelon1,2*, Takahiko Mukaino1, Jun Yokoyama1, Taira Uehara2, Katsuya Ogata2, Jun-ichi Kira1 and Shozo Tobimatsu2 1Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan2Department of Clinical Neurophysiology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Background: Semi-quantitative electroencephalogram (EEG) analysis is easy to perform and has been used to differentiate dementias, as well ...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
This study aimed to investigate white matter microstructure alterations by using connectometry in patients with PD-EDS, in comparison to PD-nEDS and healthy individuals. Materials and Methods Participants Participants involved in this research were recruited from Parkinson's Progression Markers Initiative (PPMI, http://www.ppmi-info.org/). The study was approved by the institutional review board of all participating sites in Europe, including Attikon University Hospital (Greece), Hospital Clinic de Barcelona and Hospital Universitario Donostia (Spain), Innsbruck University (Austria), Paracelsus-Elena Clinic Kass...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusion: Reduced saliva SP concentrations may predict early pharyngeal swallowing dysfunction in PD patients. This finding supports the hypothesis that an impaired SP mediated neurotransmission has a significant impact for the development of dysphagia in PD patients. Larger studies are needed to confirm SP as a clinical useful biomarker for early detection of PD-related dysphagia. Introduction Following Alzheimer's disease, Parkinson's disease (PD) is the second most common neurodegenerative disorder (1, 2). Oropharyngeal dysphagia is a clinically relevant symptom in affected patients as the majori...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusions Dysautonomic symptoms frequently occuring in α-synucleinopathies comprise cardiovascular, gastrointestinal, urogenital and thermoregulatory disturbances. These symptoms reduce quality of life and worsen prognosis. The understanding of their pathophysiology, as well as the detection of α-synuclein deposition and autonomic dysfunction in the premotor stages of α-synucleinopathies may be key for identifying novel treatment targets and improving clinical outcomes. While causative treatment is not yet available, improvement of quality of life can be achieved by personalized symptomatic treatment r...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
This study underscores the importance of chronic stimulation in the modulation of sensorimotor integration and proprioception. The authors considered two possible mechanisms underlying SAI modulation by STN DBS. High-frequency DBS of the STN might normalize synchronization between basal ganglia structures, which might restore the ability of thalamocortical relay cells to respond to depolarizing inputs involved in sensorimotor integration (Brown et al., 2001; Rubin and Terman, 2004). Alternatively, STN DBS might have a direct effect on cortical structures through antidromic stimulation of the cortico-subthalamic pathway. I...
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
AbstractAdult-onset neurodegenerative disorders, like Parkinson ’s disease (PD) and dementia with Lewy bodies (DLB), that share the accumulation of aggregated α-synuclein (αSynagg) as their hallmark molecular pathology are collectively known as α-synucleinopathies. Diagnosing α-synucleinopathies requires the post-mortem detection of αSynagg in various brain regions. Recent efforts to measure αSynagg in living patients include quantifying αSynagg in different biofluids as a biomarker for PD. We adopted the real-time quaking-induced conversion (RT-QuIC) assay to detect very low...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSION: Today the role of MRI is no longer limited to ruling out underlying causes of cognitive deterioration. MRI can show patterns of atrophy with a predictive value for certain dementias which, although not specific or unique to each disease, can help to confirm diagnostic suspicion or to identify certain processes. For this reason, it is important for radiologists to know the characteristic findings of the most common dementias. PMID: 29903629 [PubMed - as supplied by publisher]
Source: Radiologia - Category: Radiology Authors: Tags: Radiologia Source Type: research
Conclusion D2 antagonism by (-)-eticlopride at high dose (0.03 mg/kg) dramatically increased striatal uptake of [18F]VAT in NHPs, suggesting PET with [18F]VAT provides a useful tool for investigation of dopaminergic modulation on VAChT expression in the brain of living animals. The elevation of striatal [18F]VAT uptake by 0.03 mg/kg (-)-eticlopride might be attributed to the disinhibition of cholinergic transmission by D2 antagonism. Ongoing studies are exploring the impact of D2 agonism on VAChT expression in the NHP brain. These results may help guide future investigation of the effects of dopaminergic drugs on cholinerg...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Science III Source Type: research
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