TY - JOUR
T1 - Irreversible dimerization/tetramerization and post-translational modifications inhibit proteolytic degradation of Aβ peptides of Alzheimer's disease
AU - Kuo, Yu Min
AU - Webster, Scott
AU - Emmerling, Mark R.
AU - De Lima, Nettie
AU - Roher, Alex E.
N1 - Funding Information:
This work was in part supported by the NIH grant AG11925.
PY - 1998/4/28
Y1 - 1998/4/28
N2 - Experimental evidence increasingly implicates the β-amyloid peptide in the pathogenesis of Alzheimer's disease. β-amyloid filaments dramatically accumulate in the neuritic plaques and vascular deposits as the result of the brain's inability to clear these structures. In this paper, we demonstrate that in addition to the intrinsic stability of AβN-42, the time dependent generation of irreversibly associated Aβ dimers and tetramers incorporated into Aβ filaments are themselves resistant to proteolytic degradation. The presence of post-translational modifications such as isomerization of aspartyls 1 and 7, cyclization of glutamyl 3 to pyroglutamyl and oxidation of methionyl 35, further contribute to the insolubility and stability of Aβ. All these factors promote the accumulation of neurotoxic amyloid in the brains of patients with Alzheimer's disease, and should be considered in therapeutic strategies directed towards the dissociation of the brain's Aβ filaments. Copyright (C) 1998 Elsevier Science B.V.
AB - Experimental evidence increasingly implicates the β-amyloid peptide in the pathogenesis of Alzheimer's disease. β-amyloid filaments dramatically accumulate in the neuritic plaques and vascular deposits as the result of the brain's inability to clear these structures. In this paper, we demonstrate that in addition to the intrinsic stability of AβN-42, the time dependent generation of irreversibly associated Aβ dimers and tetramers incorporated into Aβ filaments are themselves resistant to proteolytic degradation. The presence of post-translational modifications such as isomerization of aspartyls 1 and 7, cyclization of glutamyl 3 to pyroglutamyl and oxidation of methionyl 35, further contribute to the insolubility and stability of Aβ. All these factors promote the accumulation of neurotoxic amyloid in the brains of patients with Alzheimer's disease, and should be considered in therapeutic strategies directed towards the dissociation of the brain's Aβ filaments. Copyright (C) 1998 Elsevier Science B.V.
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U2 - 10.1016/S0925-4439(98)00014-3
DO - 10.1016/S0925-4439(98)00014-3
M3 - Article
C2 - 9630681
AN - SCOPUS:0031862969
VL - 1406
SP - 291
EP - 298
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 3
ER -