b-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 b-amyloid senile plaques (SP) and intraneuronal tau-rich neurofibrillary tangles (NFT) are seen. SP form by the extracellular accumulation of amyloid beta (Ab) peptide into amyloid deposits, with the Ab42 form being most prominant. Proteolytic enzymes b-secretase and g-secretase sequentially cleave the b-amyloid precursor protein (APP) into Ab. The enzyme BACE (b-site APP cleaving enzyme) has been identified as b-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.

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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).