Interface between tauopathies and synucleinopathies: A tale of two proteins

@article{Galpern2006InterfaceBT,
  title={Interface between tauopathies and synucleinopathies: A tale of two proteins},
  author={Wendy R. Galpern and Anthony E. Lang},
  journal={Annals of Neurology},
  year={2006},
  volume={59}
}
Neurodegenerative diseases are often classified based on the abnormal accumulation of synuclein or tau. Traditionally, these disorders have been viewed as distinct clinical and pathological entities. However, advances in molecular genetics and protein biochemistry have shown intriguing overlaps. The most common synucleinopathy, Parkinson's disease, is characterized by extrapyramidal motor dysfunction, whereas the most common tauopathy, Alzheimer's disease, is defined by dementia. Yet there is… 

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References

SHOWING 1-10 OF 145 REFERENCES

alpha-Synuclein is phosphorylated in synucleinopathy lesions.

It is shown by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions and promoted fibril formation in vitro.

α-Synuclein is phosphorylated in synucleinopathy lesions

It is shown by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of α-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions and promoted fibril formation in vitro.

The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia

Dementia with Lewy bodies is related to mutation of α‐synuclein, and the novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid in a much conserved area of the protein, is likely to produce severe disturbance of protein function.

Tau and alpha-synuclein pathology in amygdala of Parkinsonism-dementia complex patients of Guam.

The amygdala may be selectively vulnerable to developing both tau and alpha-synuclein pathology or tau pathology may predispose it to synuclein aggregation, thereby implicating the aggregation of these molecules in the severe neurodegeneration frequently observed in this location.

Lewy body-related α-synucleinopathy in the aged human brain

  • K. Jellinger
  • Biology, Medicine
    Journal of Neural Transmission
  • 2004
The findings largely confirm Braak’s staging of LB-pathology in PD and suggest morphologic and pathogenic relations between PD (brainstem type) and DLB with and without coexistent AD pathology.

Lewy body-related alpha-synucleinopathy in the aged human brain.

  • K. Jellinger
  • Biology, Psychology
    Journal of neural transmission
  • 2004
The basic mechanisms of LB-related AS-pathology and their pathogenic and clinical relevance in aged brain and neurodegenerative disorders await further elucidation, suggesting morphologic similarities betwee these disorders.

Phosphorylated alpha-synuclein is ubiquitinated in alpha-synucleinopathy lesions.

The biochemical characteristics of the additional, higher molecular mass species of phosphorylated alpha-synuclein-positive polypeptides that also are recovered in the Sarkosyl-insoluble fraction of synucleinopathy and migrate at about 22 and 29 kDa strongly suggest that phosphorylations are targeted to mono- and diubiquitination in syn nucleinopathy brains, which may have implications for mechanisms of these diseases.

α-Synuclein in Familial Alzheimer Disease: Epitope Mapping Parallels Dementia With Lewy Bodies and Parkinson Disease

These findings support the hypothesis that the mechanism of α-synuclein aggregation is the same within cell types but distinctive between cell types, and suggest that the epitope profiles in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway.
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