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P4‐028: ZINC‐INDUCED DIMERS OF CHEMICALLY MODIFIED A β‐ ARE POSSIBLE AGGREGATION SEEDS
Author(s) -
Kozin Sergey A.,
Tsvetkov Philippe,
Kulikova Alexandra,
Indeikina Maria,
Mezentsev Yuri,
Istrate Andrey,
Popov Igor,
Ivanov Alexis,
Polshakov Vladimir,
Makarov Alexander
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1542
Subject(s) - isothermal titration calorimetry , zinc , chemistry , circular dichroism , peptide , biophysics , tetrapeptide , dimer , nuclear magnetic resonance spectroscopy , stereochemistry , crystallography , biochemistry , organic chemistry , biology
to b-amyloid (ELISA) and cooperative viral neutralizing activity of SP-D and b-amyloid. Recombinantly modified versions of the SP-D binding domain were also tested for interactions with b-amyloid. Results: Several fragments of b -amyloid (i.e. peptides 1-42, 1-34, 35-42) had viral neutralizing and aggregating activity and also were able to aggregate bacteria and increase uptake of influenza virus and bacteria by human neutrophils. The carbohydrate binding domain of SP-D bound to b -amyloid (1-42) in a dose dependent manner. Some modified versions of the SP-D binding domain had increased binding to b -amyloid. Combining the SP-D binding domain with b -amyloid (1-42) resulted in additive viral neutralization. Conclusions: These findings demonstrate that several fragments of b-amyloid have antiviral activity and also can induce viral and bacterial aggregation and modify neutrophil uptake of pathogens. SP-D is known to have similar activities and we now show that it can bind to b-amyloid. SP-D and b-amyloid separately or together could be important innate immune effectors in the central nervous system. T he SP-D binding domain can be modified to increase binding to b-amyloid. This approach could possibly be exploited to aid clearance of b-amyloid.