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The Synucleinopathies: Twenty Years On.

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TLDR
The work, which led to the identification of α-synuclein in Lewy bodies, Lewy neurites and Papp-Lantos bodies, is reviewed as well as what has happened since.
Abstract
In 2017, it is two hundred years since James Parkinson provided the first complete clinical description of the disease named after him, fifty years since the introduction of high-dose D,L-DOPA treatment and twenty years since α-synuclein aggregation came to the fore. In 1998, multiple system atrophy joined Parkinson’s disease and dementia with Lewy bodies as the third major synucleinopathy. Here we review our work, which led to the identification of α-synuclein in Lewy bodies, Lewy neurites and Papp-Lantos bodies, as well as what has happened since. Some of the experiments described were carried out in collaboration with ML Schmidt, VMY Lee and JQ Trojanowski.

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Mechanisms of tissue and cell-type specificity in heritable traits and diseases

TL;DR: The large prevalence of tissue-selective traits and diseases is discussed, common molecular mechanisms underlying their tissue- selective manifestation are described and computational strategies and publicly available resources for elucidating the molecular basis of their genotype–phenotype relationships are presented.
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Biophysical processes underlying cross-seeding in amyloid aggregation and implications in amyloid pathology.

TL;DR: This review article focuses on the biophysical processes underlying the cross-seeding for some of the most commonly studied amyloid proteins, including hIAPP, human islet amyloids polypeptide (hIAPP), and alpha-synuclein.
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Tau filaments in neurodegenerative diseases

TL;DR: It is shown that high‐resolution structures of Tau filaments from human brain can be determined by electron cryo‐microscopy, and these filaments may form the seeds that underlie the prion‐like properties of aggregated tau.
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How specific are the conformation-specific α-synuclein antibodies? Characterization and validation of 16 α-synuclein conformation-specific antibodies using well-characterized preparations of α-synuclein monomers, fibrils and oligomers with distinct structures and morphology.

TL;DR: The findings suggest that the great majority of α-syn aggregate-specific antibodies do not differentiate between oligomers and fibrils, thus highlighting the importance of exercising caution when interpreting results obtained using these antibodies.
References
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Journal ArticleDOI

Staging of brain pathology related to sporadic Parkinson’s disease

TL;DR: This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
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Mutation in the α-synuclein gene identified in families with Parkinson's disease

TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
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Alpha-synuclein in Lewy bodies.

TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
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Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis

TL;DR: It is proposed that this chemical selectively damages cells in the substantia nigra in patients who developed marked parkinsonism after using an illicit drug intravenously.
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