Membrane alterations as causes of impaired signal transduction in Alzheimer's disease and aging.
Changes in cell-membrane composition in normal aging and in Alzheimer's and other age-related diseases appear to result in impaired neurotransmitter-triggered signal transduction. The impaired signal transduction seems to be related to dysfunctions in the coupling of G proteins to their receptors and effectors. Direct demonstration of altered physiochemical properties of brain tissue of patients with Alzheimer's disease has been achieved by small-angle X-ray diffraction. In this disease, thinner membranes correlate with a 30% decrease in moles of cholesterol:phospholipid. Such changes can affect directly the coupling and uncoupling properties of G proteins, and can account for signal transduction deficits. These findings offer a complementary alternative to the beta-amyloid hypothesis, and an opportunity to consider new types of therapeutic interventions.
Roth
G S
GS
Molecular Physiology and Genetics Section, National Institute on Aging, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA.
Joseph
J A
JA
Mason
R P
RP
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008566:Membranes / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction
D018377:Neurotransmitter Agents; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins