Potential inplications of endogenous aldehydes in beta-amyloid misfolding, oligomerization and fibrillogenesis.
J Neurochem
; 99(5): 1413-24, 2006 Dec.
Article
in En
| MEDLINE
| ID: mdl-17074066
ABSTRACT
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 beta-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 beta-amyloid at different stages, i.e. beta-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 beta-amyloid beta-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 beta-amyloid deposition is discussed.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Amyloid beta-Peptides
/
Neurofibrillary Tangles
/
Aldehydes
/
Alzheimer Disease
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Neurochem
Year:
2006
Document type:
Article
Affiliation country:
Canada