The role of cardiac 123 I‐metaiodobenzylguanidine scintigraphy in multiple system atrophy

2020 ◽  
Vol 20 (5) ◽  
pp. 811-811
Author(s):  
Divyani Garg
Keyword(s):  
Multiple System Atrophy ◽  
Metaiodobenzylguanidine Scintigraphy

scholarly journals Multiple system atrophy: genetic risks and alpha-synuclein mutations

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2072 ◽  
Author(s):  
Heather T Whittaker ◽  
Yichen Qui ◽  
Conceição Bettencourt ◽  
Henry Houlden
Keyword(s):  
Multiple System Atrophy ◽  
Protein Misfolding ◽  
Research Collaboration ◽  
Late Onset ◽  
Alpha Synuclein ◽  
Common Mechanism ◽  
International Research Collaboration ◽  
Cytoplasmic Inclusions ◽  
Genetic Risks

Multiple system atrophy (MSA) is one of the few neurodegenerative disorders where we have a significant understanding of the clinical and pathological manifestations but where the aetiology remains almost completely unknown. Research to overcome this hurdle is gaining momentum through international research collaboration and a series of genetic and molecular discoveries in the last few years, which have advanced our knowledge of this rare synucleinopathy. In MSA, the discovery of α-synuclein pathology and glial cytoplasmic inclusions remain the most significant findings. Families with certain types of α-synuclein mutations develop diseases that mimic MSA, and the spectrum of clinical and pathological features in these families suggests a spectrum of severity, from late-onset Parkinson’s disease to MSA. Nonetheless, controversies persist, such as the role of common α-synuclein variants in MSA and whether this disorder shares a common mechanism of spreading pathology with other protein misfolding neurodegenerative diseases. Here, we review these issues, specifically focusing on α-synuclein mutations.

scholarly journals The emerging role of α-synuclein truncation in aggregation and disease

2020 ◽  
Vol 295 (30) ◽  
pp. 10224-10244 ◽  
Author(s):  
Zachary A. Sorrentino ◽  
Benoit I. Giasson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Lewy Body ◽  
Critical Role ◽  
Lewy Body Dementia ◽  
Proteolytic Processing ◽  
Neuronal Protein ◽  
Preventative Strategy

α-Synuclein (αsyn) is an abundant brain neuronal protein that can misfold and polymerize to form toxic fibrils coalescing into pathologic inclusions in neurodegenerative diseases, including Parkinson's disease, Lewy body dementia, and multiple system atrophy. These fibrils may induce further αsyn misfolding and propagation of pathologic fibrils in a prion-like process. It is unclear why αsyn initially misfolds, but a growing body of literature suggests a critical role of partial proteolytic processing resulting in various truncations of the highly charged and flexible carboxyl-terminal region. This review aims to 1) summarize recent evidence that disease-specific proteolytic truncations of αsyn occur in Parkinson's disease, Lewy body dementia, and multiple system atrophy and animal disease models; 2) provide mechanistic insights on how truncation of the amino and carboxyl regions of αsyn may modulate the propensity of αsyn to pathologically misfold; 3) compare experiments evaluating the prion-like properties of truncated forms of αsyn in various models with implications for disease progression; 4) assess uniquely toxic properties imparted to αsyn upon truncation; and 5) discuss pathways through which truncated αsyn forms and therapies targeted to interrupt them. Cumulatively, it is evident that truncation of αsyn, particularly carboxyl truncation that can be augmented by dysfunctional proteostasis, dramatically potentiates the propensity of αsyn to pathologically misfold into uniquely toxic fibrils with modulated prion-like seeding activity. Therapeutic strategies and experimental paradigms should operate under the assumption that truncation of αsyn is likely occurring in both initial and progressive disease stages, and preventing truncation may be an effective preventative strategy against pathologic inclusion formation.

Role of TPPP/p25 on α-synuclein-mediated oligodendroglial degeneration and the protective effect of SIRT2 inhibition in a cellular model of multiple system atrophy☆

2010 ◽  
Vol 57 (8) ◽  
pp. 857-866 ◽  
Author(s):  
Takafumi Hasegawa ◽  
Toru Baba ◽  
Michiko Kobayashi ◽  
Masatoshi Konno ◽  
Naoto Sugeno ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Protective Effect ◽  
Cellular Model

scholarly journals Single Nuclei Sequencing of Human Putamen Oligodendrocytes Reveals Altered Heterogeneity and Disease-Associated Changes in Parkinson's Disease and Multiple System Atrophy

2021 ◽  
Author(s):  
Erin Teeple ◽  
Pooja Joshi ◽  
Rahul S. Pande ◽  
Yinyin Huang ◽  
Akshat Karambe ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Functional Enrichment ◽  
Cell Level ◽  
Parkinsons Disease ◽  
Unfolded Protein ◽  
Pathway Gene ◽  
Healthy Control ◽  
Protein Response ◽  
New Strategies

The role of oligodendrocytes in neurodegenerative diseases remains incompletely understood and largely unexplored at the single cell level. We profiled 87,086 single nuclei from human brain putamen region for healthy control, Parkinsons Disease (PD), and Multiple System Atrophy (MSA). Oligodendrocyte lineage cells were the dominant cell-type in the putamen with oligodendrocyte subpopulations clustered by transcriptomic variation found to exhibit diverse functional enrichment patterns, and this oligodendrocyte heterogeneity was altered in a disease-specific way. Among profiled oligodendrocyte subpopulations, differences in expression of SNCA, HAPLN2, MAPT, APP, and OPALIN were observed for PD and MSA compared with healthy controls. Intriguingly, greater activation of unfolded protein response pathway gene expression was observed in PD nuclei versus MSA. Using network analysis, we then identified specific PD- and MSA-correlated gene co-expression modules enriched with disease relevant pathways; the PD-correlated module was significantly enriched for Parkinsons Disease GWAS loci (p = 0.01046). Our analysis provides a broader understanding of oligodendrocyte heterogeneity and reveals distinctive oligodendrocyte pathological alterations associated with PD and MSA which may suggest potential novel therapeutic targets and new strategies for disease modification.

scholarly journals REM Sleep Behaviour Disorder in Multiple System Atrophy: From Prodromal to Progression of Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Giulia Giannini ◽  
Federica Provini ◽  
Pietro Cortelli ◽  
Giovanna Calandra-Buonaura
Keyword(s):  
Multiple System Atrophy ◽  
Rem Sleep ◽  
Autonomic Failure ◽  
Disease Onset ◽  
Behaviour Disorder ◽  
Sleep Behaviour ◽  
Disease Modifying Therapies ◽  
Rem Sleep Behaviour Disorder ◽  
Progression Of Disease

A higher frequency of motor and breathing sleep-related disorders in multiple system atrophy (MSA) populations is reported. REM sleep behaviour disorder (RBD) is one of the most robust markers of an underlying alpha-synucleinopathy. Although a large corpus of literature documented the higher prevalence of RBD in MSA, few studies have systematically investigated the prevalence of RBD as mode of disease onset and its role in disease progression. Moreover, there has been increasing interest in phenoconversion into synucleinopathies of cohorts of patients with isolated RBD (iRBD). Finally, some studies investigated RBD as predictive factor of conversion in isolated autonomic failure, a synucleinopathy presenting with autonomic failure as the sole clinical manifestation that could convert to a manifest central nervous system synucleinopathy. As the field of neurodegenerative disorders moves increasingly towards developing disease-modifying therapies, detecting individuals in the prodromal stage of these synucleinopathies becomes crucial. The aims of this review are to summarise (1) the prevalence of RBD during the course of MSA and as presenting feature of MSA (iRBD), (2) the RBD features in MSA, (3) MSA progression and prognosis in the subgroup of patients with RBD predating disease onset, and (4) the prevalence of MSA conversion in iRBD cohorts. Moreover, we summarise previous results on the role of RBD in the context of isolated autonomic failure as marker of phenoconversion to other synucleinopathies and, in particular, to MSA.

[123I]β-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson’s disease and multiple system atrophy

2003 ◽  
Vol 42 (01) ◽  
pp. 31-38 ◽  
Author(s):  
Th. Brücke ◽  
P. Odin ◽  
D. J. Brooks ◽  
H. Kolbe ◽  
P. Gielow ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Yahr Stage ◽  
Advanced Parkinson’S Disease ◽  
Affected Side ◽  
Duration Of Disease ◽  
Definition Of ◽  
Mesial Frontal Cortex

Summary Aims: Definition of the regional pattern of dopamine transporter (DAT) dysfunction in advanced Parkinson’s disease (PD) and evaluation of a potential correlation between DAT binding and symptoms; elucidation of the role of DAT imaging in the differential diagnosis of PD and multiple system atrophy (MSA); assessment and comparison of serotonin transporter (SERT) binding in PD and MSA. Methods: [123I]ß-CIT SPECT was performed in 14 patients with advanced PD, 10 with moderate MSA and 20 healthy persons. Specific to nonspecific tracer binding ratios (V3’’) were calculated via ROI analysis of uptake images at 4 h (SERT binding) and 24 h (DAT binding) p. i. Results: In PD bilateral reduction of striatal DAT binding (63-70%) was seen. The caudate ipsilateral to the clinically predominantly affected side showed relatively the least impairment. Significant correlations (r = -0.54 to -0.64) between DAT binding and Hoehn and Yahr stage, UPDRS-scores and duration of disease were found. In MSA DAT binding was less reduced (40-48%) targeting the putamen contralateral to the side of clinical predominance. Significantly lower SERT binding was observed in PD midbrain and MSA hypothalamus compared to controls – and in MSA relative to PD mesial frontal cortex. Conclusions: In advanced PD striatal DAT binding is markedly reduced with the least reduction in caudate ipsilateral to the clinically predominantly affected side. In moderate MSA with asymmetrical symptoms DAT dysfunction is predominant in the contralateral putamen, a pattern seen in early PD. The reduction of SERT in the midbrain area of PD patients suggests additional tegmental degeneration while in MSA the serotonergic system seems to be more generally affected.

The Potential Role of Gut-Derived Inflammation in Multiple System Atrophy

2017 ◽  
Vol 7 (2) ◽  
pp. 331-346 ◽  
Author(s):  
Phillip A. Engen ◽  
Hemraj B. Dodiya ◽  
Ankur Naqib ◽  
Christopher B. Forsyth ◽  
Stefan J. Green ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Potential Role

Role of intestinal peptides and the autonomic nervous system in postprandial hypotension in patients with multiple system atrophy

2012 ◽  
Vol 260 (2) ◽  
pp. 475-483 ◽  
Author(s):  
Takeshi Fukushima ◽  
Masato Asahina ◽  
Yoshikatsu Fujinuma ◽  
Yoshitaka Yamanaka ◽  
Akira Katagiri ◽  
...  
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Multiple System Atrophy ◽  
Postprandial Hypotension ◽  
Autonomic Nervous ◽  
Intestinal Peptides
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