How mutations that lead to Alzheimer's Disease affect calcium levels in neurons

Frank LaFerla, PhD
Regents of the Univ. of California (Irvine, CA)
Year Awarded:
2000
Grant Duration:
April 1, 2000 to March 31, 2002
Disease:
Alzheimer's Disease
Award Amount:
$171,216
Grant Reference ID:
A2000005
Award Type:
Standard
Award Region:
US Southwestern

Calcium Dyshomeostasis Induced by Presenilin Mutations

Details

It is known that changes in intracellular calcium cause neuronal cell death and increase the production of beta amyloid, the protein that accumulates to form brain plaques. Dr. Laferla has found that mutations in Presenilin 1 and 2 that cause the early onset of AD also cause changes in intracellular calcium. He is now examining the possible role of the presenilin genes in regulating calcium levels. Utilizing a variety of methodologies and experimental systems for this work, he hopes to increase our understanding of the function of presenilin and its role in AD.

Publications

Leissring, M.A., LaFerla, F.M., Callamaras, N., and Parker, I. (2001) Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling. Neurobiology of Disease. 8(3):469-78.

Leissring, M.A., Akbari, Y., Fanger, C.M., Cahalan, M., Mattson, M.P., and LaFerla, F.M. (2000) Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knock-in mice. Journal of Cell Biology. 149:793-798.

Leissring, M.A., Yamasaki, T.R., Wasco, W., Buxbaum, J.D., Parker, I., and LaFerla, F.M. (2000) Calsenilin reverses presenilin-mediated enhancement of calcium signaling. Proceedings of the National Academy of Sciences U.S.A. 97:8590-8593.

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