Newfound effect of N-acetylaspartate in preventing and reversing aggregation of amyloid-beta in vitro

NEUROBIOLOGY OF DISEASE

卷:117

Article

Dolle, Jean-Pierre¹  Rodgers, Jeffrey M.²  Browne, Kevin D.¹  Troxler, Thomas²  Gai, Feng²  Smith, Douglas H.¹ 

[1] Univ Penn, Dept Neurosurg, Penn Ctr Brain Injury & Repair, 220 South 33rd St,283 Towne Bldg, Philadelphia, PA 19104 USA

[2] Univ Penn, Ultrafast Opt Proc Lab, Dept Chem, Philadelphia, PA 19104 USA

关键词: N-Acetylaspartate;    Amyloid beta;    Aggregation inhibitor;    Thioflavin-T;    Fluorescence correlation spectroscopy;    Dynamic light scattering;    Transmission electron microscopy;   

DOI  :  10.1016/j.nbd.2018.05.023

来源: Elsevier

【 摘 要 】

Although N-acetylaspartate (NAA) has long been recognized as the most abundant amino acid in neurons by far, its primary role has remained a mystery. Based on its unique tertiary structure, we explored the potential of NAA to modulate aggregation of amyloid-beta (A beta) peptide 1-42 via multiple corroborating aggregation assays along with electron microscopy. Thioflavin-T fluorescence assay demonstrated that at physiological concentrations, NAA substantially inhibited the initiation of A beta) fibril formation. In addition, NAA added after 25 min of A beta) aggregation was shown to break up preformed fibrils. Electron microscopy analysis confirmed the absence of mature fibrils following NAA treatment. Furthermore, fluorescence correlation spectroscopy and dynamic light scattering measurements confirmed significant reductions in A beta) fibril hydrodynamic radius following treatment with NAA. These results suggest that physiological levels of NAA could play an important role in controlling A beta) aggregation in vivo where they are both found in the same neuronal compartments.

【 授权许可】

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