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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
Abnormal alpha-synuclein solubility, aggregation and nitration in the frontal cortex in Pick's disease
Esther Dalfó1, Anna Martinez, Gerard Muntané
1Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL/Hospital Universitari de Bellvitge, carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain.
Neuroscience Letters
|March 7, 2006
Summary
Pick's disease (PiD) shows abnormal alpha-synuclein solubility and aggregation in the frontal cortex. This differs from Lewy body diseases and involves nitrated alpha-synuclein without Lewy body formation.
Area of Science:
- Neuroscience
- Neuropathology
- Biochemistry
Background:
- Alpha-synuclein aggregation is implicated in neurodegenerative diseases.
- Pick's disease (PiD) is a tauopathy, but alpha-synuclein pathology is increasingly recognized.
- Distinct patterns of alpha-synuclein pathology may differentiate neurodegenerative conditions.
Purpose of the Study:
- To investigate alpha-synuclein solubility and aggregation in the frontal cortex of PiD cases.
- To compare alpha-synuclein patterns in PiD with those in Lewy body diseases (LBD).
- To examine alpha-synuclein nitration in relation to PiD vulnerability.
Main Methods:
- Western blotting of SDS-soluble fractions from frontal cortex tissue.
- Immunoblotting using antibodies against nitrated alpha-synuclein.
- Comparison with cerebral cortex tissue from age-matched controls and LBD cases.
Main Results:
- Abnormal alpha-synuclein solubility and aggregation (45 kDa and higher bands) were detected in PiD frontal cortex, distinct from LBD.
- Nitrated alpha-synuclein (45 and 60 kDa bands) was found in soluble fractions of the PiD-vulnerable frontal cortex but not the resistant occipital cortex.
- Nitrated alpha-synuclein was diffusely cytoplasmic in PiD neurons, unlike the Lewy body localization in synucleinopathies.
Conclusions:
- Pick's disease exhibits abnormal and distinct alpha-synuclein solubility and aggregation in the frontal cortex.
- Alpha-synuclein nitration occurs in PiD, particularly in vulnerable brain regions, without Lewy body formation.
- These findings highlight unique alpha-synuclein biochemical alterations in PiD, differentiating it from synucleinopathies.
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