scholarly journals Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders

2017 ◽  
Vol 18 (7) ◽  
pp. 733-745 ◽  
Author(s):  
Yun-Tzai C. Lee ◽  
Shang-Te D. Hsu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Post Translational Modifications

scholarly journals Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson’s Disease and Neurodegenerative Disorders

2016 ◽  
Author(s):  
Yun-Tzai Cloud Lee ◽  
Shang-Te Danny Hsu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Lewy Bodies ◽  
Modern Society ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Inclusions ◽  
Biophysical Studies ◽  
The Impact

AbstractParkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carbonyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCH-L1 and PD in terms of loss of cellular functions or gain of cellular toxicity.

scholarly journals Imaging Familial and Sporadic Neurodegenerative Disorders Associated with Parkinsonism

2021 ◽  
Author(s):  
David J. Brooks
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Lewy Body Dementia ◽  
Imaging Biomarkers ◽  
Imaging Findings ◽  
Subclinical Disease ◽  
Similarities And Differences ◽  
Potential Use

AbstractIn this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson’s disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with nonmotor complications of PD are presented. The similarities and differences in imaging findings in Lewy body dementia, Parkinson’s disease dementia, and Alzheimer’s disease are discussed.

scholarly journals Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Focused Ultrasound ◽  
Temporal Cortex ◽  
Clinical State ◽  
Cognitive Improvement ◽  
Bbb Opening

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

scholarly journals Response to Telemedicine Visits From Patients With Parkinsonism During the COVID-19 Pandemic on Postvisit Surveys

2021 ◽  
Vol 8 ◽  
pp. 237437352199722
Author(s):  
Wissam Deeb ◽  
Christopher W Hess ◽  
Noheli Gamez ◽  
Bhavana Patel ◽  
Kathryn Moore ◽  
...  
Keyword(s):  
Older Adults ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Tertiary Care ◽  
Specialty Clinic ◽  
Cognitive Limitations ◽  
Time Savings ◽  
Ease Of Access ◽  
Almost All

Parkinson’s disease and parkinsonism are common chronic neurodegenerative disorders that tend to affect older adults and cause physical and sometimes cognitive limitations. Given that these limitations could impact successful telemedicine use, we aimed to investigate the experiences of patients with parkinsonism using telemedicine during the COVID-19 pandemic. A 19-item survey was emailed to patients with parkinsonism following telemedicine visits at a single US tertiary care parkinsonism specialty clinic. Seventy-four individuals responded, out of 270 invitations sent. Almost two-thirds (61.6%) of the respondents were comfortable with using technology in general, and almost all were very satisfied with their telemedicine experience. The most commonly reported benefits included cost and travel savings, ease of access to a specialist, and time savings. Issues with technology and previsit instructions were the most commonly identified challenges (28%). Urgent implementation, due to the pandemic, of telemedicine care for patients with parkinsonism was feasible and well received. The challenges most commonly reported by patients could be potentially alleviated by better education and support.

scholarly journals Subcellular orchestration of alpha-synuclein variants in Parkinson’s disease brains revealed by 3D multicolor STED microscopy

2018 ◽  
Author(s):  
Tim E. Moors ◽  
Christina A. Maat ◽  
Daniel Niedieker ◽  
Daniel Mona ◽  
Dennis Petersen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Distribution Patterns ◽  
Alpha Synuclein ◽  
Label Free ◽  
Post Translational Modifications ◽  
Sted Microscopy ◽  
C Terminus

AbstractPost-translational modifications of alpha-synuclein (aSyn), particularly phosphorylation at Serine 129 (Ser129-p) and truncation of its C-terminus (CTT), have been implicated in Parkinson’s disease (PD) pathology. To gain more insight in the relevance of Ser129-p and CTT aSyn under physiological and pathological conditions, we investigated their subcellular distribution patterns in normal aged and PD brains using highly-selective antibodies in combination with 3D multicolor STED microscopy. We show that CTT aSyn localizes in mitochondria in PD patients and controls, whereas the organization of Ser129-p in a cytoplasmic network is strongly associated with pathology. Nigral Lewy bodies show an onion skin-like architecture, with a structured framework of Ser129-p aSyn and neurofilaments encapsulating CTT aSyn in their core, which displayed high content of proteins and lipids by label-free CARS microscopy. The subcellular phenotypes of antibody-labeled pathology identified in this study provide evidence for a crucial role of Ser129-p aSyn in Lewy body formation.

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