Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch Paperα-synuclein phosphorylation and truncation are normal events in the adult human brain
Highlights
▶αsynuclein protein levels are lower in the human substantia nigra and nucleus basalis of Meynert compared with other brain regions. ▶The reduction in α-synuclein protein levels in these two human brain regions is independent of age and pathology. ▶Phosphorylated α-synuclein is increased in substantia nigra and nucleus basalis of Meynert, inversely correlating with the total amount of α-synuclein. ▶Truncated α-synuclein is a general event present in normal and Lewy body disease brains and is not related to pathology or age.
Section snippets
Human brain samples
The brains of 13 patients were obtained at autopsy following informed consent of the patients or their relatives and the approval of the local ethics committee. Eight different areas were dissected, frozen on dry ice, and stored at −80 °C until use. The areas were frontal cortex (area 8), temporal cortex (anterior part of the superior gyrus), caudate (head), putamen (medial), nucleus basalis of Meynert, amygdala, substantia nigra, and cerebellum (upper vermis). Both genders were equally
α-synuclein levels in human samples
Total levels of α-synuclein were studied by Western blotting in eight regions of 13 human cases classified according to their clinical and pathological identification in three groups: control (C), tauopathies (T; including AD-related and AGD cases), and Lewy body diseases (LBD); were analyzed using four different antibodies directed against different α-synuclein amino acid sequences: AB1, AB2, AB3, and AB4 (Table 2, Fig. 1). Fig. 2A shows immunodetection with all four antibodies of a
Discussion
The present results have shown that α-synuclein protein levels are lower in the substantia nigra and nucleus basalis of Meynert, which are more susceptible than other more resistant regions to Lewy body diseases. This is in agreement with previous α-synuclein mRNA studies (Rockenstein et al., 2001), but differs from other α-synuclein protein reports (Neystat et al., 1999, Kingsbury et al., 2004, Chiba-Falek et al., 2006, Tong et al., 2010). Such differences may be explained by different
Acknowledgments
This work was supported by project PETRI 2007-0397, Ministry of Science and Innovation. We are grateful to B. Wolozyn and A. Pujol for their help in providing the pcDNA 3.1 vector and reagents, respectively; and to the Proteomics Service at the Science Park of Barcelona for characterization α-synuclein by mass spectrometry. We thank T. Yohannan for editorial assistance.
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Present address: Neurodegenerative Diseases Lab., Vall d'Hebron Research Institute, Mediterranean Building, First Floor, Lab. 102, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.