Purification of α-synuclein containing inclusions from human post mortem brain tissue

McCormack, A; Chegeni, Nusha; Chegini, Fariba; Colella, Alex D.; Power, John H.; Keating, Damien J.; Chataway, Tim

doi:10.1016/j.jneumeth.2016.03.016

Cited by 24 publications

(25 citation statements)

References 15 publications

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“…GCIs of MSA are both Campbell-Switzer- and Gallyas-Braak-positive, whereas LBs are negative for Gallyas-Braak stain [ 204 ]. Purification of αS containing inclusions revealed that GCIs consist of 11.9% αS, 2.8% α-β-crystallin, and 1.7% 14-3-3 protein compared to 8.5, 2.0 and 1.5% in LBs [ 205 ]. In early disease stages, diffuse αS staining in neuronal nuclei and cytoplasm occurs in many gray matter areas, suggesting that primary aggregation of nonfibrillary αS occurs in neurons [ 141 ].…”

Section: Neuropathologymentioning

confidence: 99%

Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1

Jellinger¹

2018

JAD

151

142

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Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an α-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C). While our knowledge of the molecular pathogenesis of this devastating disease is still incomplete, updated consensus criteria and combined fluid and imaging biomarkers have increased its diagnostic accuracy. The neuropathologic hallmark of this unique proteinopathy is the deposition of aberrant α-synuclein in both glia (mainly oligodendroglia) and neurons forming glial and neuronal cytoplasmic inclusions that cause cell dysfunction and demise. In addition, there is widespread demyelination, the pathogenesis of which is not fully understood. The pathogenesis of MSA is characterized by propagation of misfolded α-synuclein from neurons to oligodendroglia and cell-to-cell spreading in a “prion-like” manner, oxidative stress, proteasomal and mitochondrial dysfunction, dysregulation of myelin lipids, decreased neurotrophic factors, neuroinflammation, and energy failure. The combination of these mechanisms finally results in a system-specific pattern of neurodegeneration and a multisystem involvement that are specific for MSA. Despite several pharmacological approaches in MSA models, addressing these pathogenic mechanisms, no effective neuroprotective nor disease-modifying therapeutic strategies are currently available. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable biomarkers and targets for effective treatment of this hitherto incurable disorder is urgently needed.

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Section: Neuropathologymentioning

confidence: 99%

Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1

Jellinger¹

2018

JAD

151

142

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“…The immunoreactivity of gci with antibodies to a-synuclein has prompted the assignment of MSA to the “synucleinopathies,” and the disease may involve a prion-like spread of a-synuclein aggregates (Jellinger and Wenning, 2016). Protein aggregation in gci involves multiple other proteins, and a-synuclein constitutes only 11.7% of the total protein (McCormack et al, 2016). …”

Section: Sporadic and Hereditary Atrophy Of The Cerebellummentioning

confidence: 99%

The neuropathology of the adult cerebellum

Koeppen

2018

Handbook of Clinical Neurology

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This chapter summarizes the neuropathologic features of nonneoplastic disorders of the adult cerebellum. Gait ataxia and extremity dysmetria are clinical manifestations of diseases that interrupt the complex cerebellar circuitry between the neurons of the cerebellar cortex, the cerebellar nuclei (especially the dentate nuclei), and the inferior olivary nuclei. The cerebellum is a prominent target of several sporadic and hereditary neurodegenerative diseases, including multiple system atrophy, spinocerebellar ataxia, and Friedreich ataxia. Purkinje cells display selective vulnerability to hypoxia but a surprising resistance to hypoglycemia. A classic toxin that damages the cerebellar cortex is methylmercury, but the most common injurious agent to Purkinje cells is ethanol. Many drugs cause ataxia, but doubts continue about phenytoin. Ischemic lesions of the cerebellum due to arterial thrombosis or embolism cause a spectrum of symptoms and signs, depending on the territory involved. Large hemorrhages have an unfavorable prognosis because they displace critical brainstem structures or penetrate into the fourth ventricle. Fungal infections and toxoplasmosis of the cerebellum, and cerebellar progressive multifocal leukoencephalopathy, have become rarer because of improved control of the acquired immunodeficiency syndrome. Ataxia is a prominent feature of prion disease. Adult-onset Niemann-Pick type C1 disease and Kufs disease may have a predominantly ataxic clinical phenotype. The adult cerebellum is also vulnerable to several leukodystrophies. A rare but widely recognized complication of cancer is paraneoplastic cerebellar degeneration.

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“…Patients lose weight even if their diet is higher in calories than that of healthy individuals at a similar age [6]. In this disease there are often problems related with an abnormal function of the gastrointestinal tract, caused mainly by disorders concerning the autonomous system [7,8]. Disorders in body composition and reduction of its mass are not beneficial from the aspect of maintenance of the health of a patient suffering from PD; therefore, its monitoring and prevention are important [9,10].…”

Section: Introductionmentioning

confidence: 99%

Body composition assessment by bioelectrical impedance analysis among patients treated with L-dopa for Parkinson’s disease

Wilczyński¹,

Półrola²

2018

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Introduction: Among the consequences of Parkinson's disease are disorders in body composition and weight loss. Aim of the research: An analysis of body composition of patients with Parkinson's disease treated with L-dopa. Material and methods: A group of 32 patients was examined, including 26 (81.25%) females and 6 (18.75%) males. The study was conducted in the Laboratory for Posturology in the Institute of Physiotherapy at the faculty of Medicine and Medical Sciences, Jan Kochanowski University in Kielce. Body composition was assessed using bioelectrical impedance analysis, which consists of the evaluation of resistance to the flow of an electric current. Results and conclusions: The majority of body composition parameters remained within the normal ranges. The mean body mass index (BMI) index in patients with Parkinson' disease was 24.12 kg/m 2 and remained within the normal range. The metabolic age of patients was 42.34 years and was considerably lower than the calendar age-54.28 years. Highly significant differences were observed between males and females according to body height (Z = 3.7541; p = 0.0002), body weight (Z = 3.2592; p = 0.0011), fat mass (%) (Z = 3.1627; p = 0.0016), fat-free mass (kg) (Z = 3.7417; p = 0.0002), muscle mass (kg) (Z = 3.7421; p = 0.0002), visceral fat (Z = 1.9892; p = 0.0467), total body water (kg), total body water content (%) (Z = 3.7428; p = 0.0002), extracellular water (kg) (Z = 3.7448; p = 0.0002), intracellular fluid (kg) (Z = 3.7424; p = 0.0002), and the ratio of extracellular water to total body water (%) (Z = 2.9223; p = 0.0035). There were also significant positive correlations between metabolic age and the Overall Stability Index (r = 0.4057, p = 0.0212) and Front-Back Stability Index (r = 0.3507, p = 0.0490). Streszczenie Wprowadzenie: Jedną z konsekwencji choroby Parkinsona są zaburzenia składu ciała i redukcja jego masy. Cel pracy: Analiza składu ciała pacjentów z chorobą Parkinsona leczonych L-dopą. Materiał i metody: Przebadano grupę 32 osób, w tym 26 (81,25%) kobiet i 6 (18,75%) mężczyzn. Badanie wykonano w Laboratorium Posturologii w Instytucie Fizjoterapii na Wydziale Lekarskim i Nauk o Zdrowiu Uniwersytetu Jana Kochanowskiego w Kielcach. Skład ciała oceniano metodą impedancji bioelektrycznej. Wyniki i wnioski: Większość parametrów składu ciała badanych mieściła się w normie. Średni wskaźnik masy ciała (BMI) pacjentów z chorobą Parkinsona wynosił 24,12 kg/m 2. Wiek metaboliczny badanych wynosił 42,34 roku i był znacz nie niższy od wieku kalendarzowego-54,28 roku. Wysoce istotne różnice między kobietami a mężczyznami dotyczyły wysokości ciała (Z =

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Purification of α-synuclein containing inclusions from human post mortem brain tissue

Cited by 24 publications

References 15 publications

Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1

Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1

The neuropathology of the adult cerebellum

Body composition assessment by bioelectrical impedance analysis among patients treated with L-dopa for Parkinson’s disease

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