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Effects of Alzheimer's Disease-Related Beta Amyloid Protein Fragments on Enzymes Metabolizing Phosphoinositides in Brain

Effects of Alzheimer's Disease-Related Beta Amyloid Protein Fragments on Enzymes Metabolizing Phosphoinositides in Brain

M A Wallace

Biochim Biophys Acta. 1994 Nov 29;1227(3):183-7.

PMID: 7986826

Abstract:

Phosphatidylinositol 4-kinase (PI 4-kinase) and phosphatidylinositol 4-phosphate kinase (PIP kinase) were assayed in membranes prepared from samples of human frontal cortex initially frozen at autopsy. PI 4-kinase activity was significantly lower in Alzheimer's disease patients relative to age-matched controls or patients with Parkinson's disease. PIP kinase was not different in Alzheimer's versus age-matched controls. The beta amyloid protein fragment 1-40 inhibited PI 4-kinase activity in assays of control human or rat cortical membranes. Fragments 1-28 and 25-35 could not mimic the effects of fragment 1-40 while a reverse peptide 40-1 was equipotent. The inhibition of PI 4-kinase by fragment 1-40 was competitive with substrate. The beta amyloid protein fragments had diverse effects on phosphoinositide-specific phospholipase C (PI-PLC) as assayed in rat cortical membranes. Low concentrations of fragment 1-40 stimulated, while high concentrations of 1-40 or 40-1 inhibited PI-PLC activity. Fragment 25-35 stimulated PI-PLC nearly 3-fold, while fragment 1-28 had only minor effects on the enzyme. The results suggest alterations in phosphoinositide metabolism in Alzheimer's disease which could affect signal transduction and/or cytoskeletal organization.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP131438794	Amyloid β Protein Fragment 1-40		131438-79-4	Price

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