α-Synuclein in Lewy bodies

Spillantini, Maria Grazia; Schmidt, Maria Luiza Gava; Lee, Virginia M.‐Y.; Trojanowski, John Q.; Jakes, Ross; Goedert, Michel

doi:10.1038/42166

Cited by 7,506 publications

(5,730 citation statements)

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“…Whereas CBS is commonly associated with early speech production deficits overlapping with progressive nonfluent aphasia (Kertesz et al, 2000), Parkinson’s disease and DLB may be associated with deficits of sentence processing and verbal working memory (Gross et al, 2012). In principle, linguistic profiles might distinguish diseases with abnormal deposition of synuclein (synucleinopathies: PDD, DLB) (Spillantini et al, 1997) from those with abnormal deposition of tau (tauopathies: CBS, PSP) (Arai et al, 2001) and the heterogeneous other pathologies underpinning CBS and progressive nonfluent aphasia (Kertesz & McMonagle, 2010). However, the potential of neuropsychological and, in particular, linguistic profiles to differentiate parkinsonian syndromes remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Verbal adynamia in parkinsonian syndromes: behavioral correlates and neuroanatomical substrate

Magdalinou¹,

Golden

Nicholas

et al. 2018

Neurocase

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Verbal adynamia (impaired language generation, as during conversation) has not been assessed systematically in parkinsonian disorders. We addressed this in patients with Parkinson’s dementia, progressive supranuclear palsy and corticobasal degeneration. All disease groups showed impaired verbal fluency and sentence generation versus healthy age-matched controls, after adjusting for general linguistic and executive factors. Dopaminergic stimulation in the Parkinson’s group selectively improved verbal generation versus other cognitive functions. Voxel-based morphometry identified left inferior frontal and posterior superior temporal cortical correlates of verbal generation performance. Verbal adynamia warrants further evaluation as an index of language network dysfunction and dopaminergic state in parkinsonian disorders.

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Section: Introductionmentioning

confidence: 99%

Verbal adynamia in parkinsonian syndromes: behavioral correlates and neuroanatomical substrate

Magdalinou¹,

Golden

Nicholas

et al. 2018

Neurocase

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“…For example, a PrP region (residues 106-126) was proposed to be crucial for prion conversion [10], and a synthetic peptide corresponding to the sequence is highly amyloidogenic and cytotoxic [11]. Some studies concentrated on the central sequence of Ab peptide, suggesting that Ab [14][15][16][17][18][19][20][21][22][23] [12] and Ab [16][17][18][19][20][21][22] [13] are the fibril-generating peptide fragments, other study indicated that the Ab 36-42 fragment could form very stable fibril with highly ordered structure and is a key factor determining the aggregation of Ab 1-42 [14]. This renders us to reconsider why only Ab 40 and Ab 42 peptides are neurotoxic and why Ab 42 aggregates into fibrils faster than Ab 40 [5].…”

Section: Introductionmentioning

confidence: 99%

Acceleration of α‐synuclein aggregation by homologous peptides

Zhang

et al. 2006

FEBS Letters

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a-Synuclein (a-Syn), amyloid b-protein and prion protein are among the amyloidogenic proteins that are associated with the neurodegenerative diseases. These three proteins share a homologous region with a consensus sequence mainly consisting of glycine, alanine and valine residues (accordingly named as the GAV motif), which was proposed to be the critical core for the fibrillization and cytotoxicity. To understand the role of the GAV motif in protein amyloidogenesis, we studied the effects of the homologous peptides corresponding to the sequence of GAV motif region (residues 66-74) on a-Syn aggregation. The result shows that these peptides can promote fibrillization of wild-type a-Syn and induce that of the charge-incorporated mutants but not the GAV-deficient a-Syn mutant. The acceleration of a-Syn aggregation by the homologous peptides is under a sequence-specific manner. The interplay between the GAV peptide and the core regions in a-Syn may accelerate the aggregation process and stabilize the fibrils. This finding provides clues for developing peptide mimics that could promote transforming the toxic oligomers or protofibrils into the inert mature fibrils.

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“…In AD, the protein tau is deposited in intracellular inclusions,2 while the amyloid beta (Aβ) peptide is in extracellular plaques. Similarly, in PD, aggregates of the protein α‐synuclein (αS) are found in Lewy bodies3 within neuronal cells. These proteins are often heavily post‐translationally modified, for example, αS undergoes phosphorylation, nitration and truncation,4, 5, 6 this makes it important to be able to characterise the real endogenous aggregates formed in cells, as these can differ from those formed by unmodified proteins.…”

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confidence: 99%

Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells

et al. 2018

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The aberrant misfolding and subsequent conversion of monomeric protein into amyloid aggregates characterises many neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. These aggregates are highly heterogeneous in structure, generally of low abundance and typically smaller than the diffraction limit of light (≈250 nm). To overcome the challenges these characteristics pose to the study of endogenous aggregates formed in cells, we have developed a method to characterise them at the nanometre scale without the need for a conjugated fluorophore. Using a combination of DNA PAINT and an amyloid‐specific aptamer, we demonstrate that this technique is able to detect and super‐resolve a range of aggregated species, including those formed by α‐synuclein and amyloid‐β. Additionally, this method enables endogenous protein aggregates within cells to be characterised. We found that neuronal cells derived from patients with Parkinson's disease contain a larger number of protein aggregates than those from healthy controls.

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α-Synuclein in Lewy bodies

Cited by 7,506 publications

References 1 publication

Verbal adynamia in parkinsonian syndromes: behavioral correlates and neuroanatomical substrate

Verbal adynamia in parkinsonian syndromes: behavioral correlates and neuroanatomical substrate

Acceleration of α‐synuclein aggregation by homologous peptides

Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells

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