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-Amyloid Plaques
SIGMA-ALDRICH
-Amyloid Plaques
Neurodegenerative diseases are a varied assortment of central nervous system disorders
characterized by neuronal loss and intraneuronal accumulations of fibrillary materials.
Abnormal protein-protein interactions may allow the precipitation of these proteins, forming
intracellular and extracellular aggregates. These abnormal interactions may play a role in
the dysfunction and death of neurons in several common neurodegenerative diseases, such
as Alzheimer’s disease (AD) and Parkinson’s disease (PD). AD is characterized by loss of
function and death of nerve cells in the brain leading to loss of cognitive function. The cause
of nerve cell death is unknown but fibrillar -amyloid senile plaques (SP) and intraneuronal
tau-rich neurofibrillary tangles (NFT) are seen. SP form by the extracellular accumulation of
amyloid beta (A) peptide into amyloid deposits, with the A42 form being most prominant.
Proteolytic enzymes -secretase and -secretase sequentially cleave the -amyloid
precursor protein (APP) into A. The enzyme BACE (-site APP cleaving enzyme) has been
identified as -secretase. NFT are made up of aggregated hyperphosphorylated tau protein.
Abnormal phosphorylation, possibly caused by mutations in the tau gene, may be one of the
events leading to aggregation.
References
Walter, J., et al., The cell biology of Alzheimer's disease : uncovering the secrets of
secretases. Curr. Opin. Neurobiol., 11, 585-590 (2001).
Esler, W.P., and Wolfe, M.S., A portrait of Alzheimer secretases - new features and familiar
faces. Science, 293, 1449-1454 (2001).
Smith, M.A., et al., Amyloid-b, tau alterations and mitochondrial dysfunction in Alzheimer
disease : the chicken or the egg? Neurochem. Int., 40, 527-531 (2002).