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Potential implications of endogenous aldehydes in β‐amyloid misfolding, oligomerization and fibrillogenesis
Author(s) -
Chen Kun,
Maley Jason,
Yu Peter H.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04181.x
Subject(s) - chemistry , methylglyoxal , biochemistry , lipid peroxidation , fibrillogenesis , malondialdehyde , circular dichroism , amyloid (mycology) , senile plaques , thioflavin , biophysics , oxidative stress , alzheimer's disease , fibril , medicine , enzyme , biology , inorganic chemistry , disease
Aldehydes are capable of inducing protein cross‐linkage. An increase in aldehydes has been found in Alzheimer's disease. Formaldehyde and methylglyoxal are produced via deamination of, respectively, methylamine and aminoacetone catalyzed by semicarbazide‐sensitive amine oxidase (SSAO, EC 1.4.3.6. The enzyme is located on the outer surface of the vasculature, where amyloidosis is often initiated. A high SSAO level has been identified as a risk factor for vascular disorders. Serum SSAO activity has been found to be increased in Alzheimer's patients. Malondialdehyde and 4‐hydroxynonenal are derived from lipid peroxidation under oxidative stress, which is also associated with Alzheimer's disease. Aldehydes may potentially play roles in β‐amyloid aggregation related to the pathology of Alzheimer's disease. In the present study, thioflavin‐T fluorometry, dynamic light scattering, circular dichroism spectroscopy and atomic force microscopy were employed to reveal the effect of endogenous aldehydes on β‐amyloid at different stages, i.e. β‐sheet formation, oligomerization and fibrillogenesis. Formaldehyde, methylglyoxal and malondialdehyde and, to a lesser extent, 4‐hydroxynonenal are not only capable of enhancing the rate of formation of β‐amyloid β‐sheets, oligomers and protofibrils but also of increasing the size of the aggregates. The possible relevance to Alzheimer's disease of the effects of these aldehydes on β‐amyloid deposition is discussed.