Cellular Membrane Fluidity in Amyloid Precursor Protein Processing

• The senile plaque is a pathologic hallmark of Alzheimer's disease (AD). Amyloid-beta peptide (A beta), the main constituent of senile plaques, is neurotoxic especially in its oligomeric form. A beta is derived from the sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases in the amyloidogenic pathway. Alternatively, APP can be cleaved by alpha-secretases within the A beta domain to produce neurotrophic and neuroprotective alpha-secretase-cleaved soluble APP (sAPP alpha) in the nonamyloidogenic pathway. Since APP and alpha-, beta-, and gamma-secretases are membrane proteins, APP processing should be highly dependent on the membrane composition and the biophysical properties of cellular membrane. In this review, we discuss the role of the biophysical properties of cellular membrane in APP processing, especially the effects of phospholipases A(2) (PLA(2)s), fatty acids, cholesterol, and A beta on membrane fluidity in relation to their effects on APP processing.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

APP

Alzheimer's disease

Cellular membrane

CYTOSOLIC PHOSPHOLIPASE A(2)

POLYUNSATURATED FATTY-ACIDS

LAURDAN

GENERALIZED POLARIZATION

ALPHA-SECRETASE CLEAVAGE

BETA ION CHANNELS

ALZHEIMERS-DISEASE

DOCOSAHEXAENOIC ACID

LIPID RAFTS

ARACHIDONIC-ACID

ENDOTHELIAL-CELLS

Neurosciences

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