Craig S. Atwood

 

 

Endocrinology of Alzheimer's Disease and Aging

E-mail: csa@medicine.wisc.edu

Research Strength: Hormonal Regulation of Aging and Neurodegenerative Diseases

Research in my laboratory draws together our interests and expertise in reproductive endocrinology and neuroscience in order to examine experimentally the hormonal regulation of aging and Alzheimer’s disease. The basic premise behind the research in my laboratory is that hormones that regulate reproduction in mammals act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence.

Based around this premise, there are a number of research themes in the laboratory. The first major theme examines the etiology of endocrine dyscrasia in regulating cognitive senescence and neurodegenerative diseases with particular reference to Alzheimer’s disease. Ongoing projects include 1) the regulation of neurosteroid synthesis in the brain and its impact on brain health and disease, 2) gene-gene association studies of the steroidogenic pathway and linkage to Alzheimer’s disease, 3) hormonal regulation of the blood-brain barrier, and 4) the hormonal regulation of AβPP and tau expression and processing. The second theme examines the hormonal regulation of embryogenesis and ongoing projects in this theme include 1) the pleiotropic functions of AβPP during human stem cell differentiation, and 2) the hormonal regulation of human embryonic stem cell proliferation and differentiation during early embryogenesis. The third major theme examines the hormonal regulation of cell cycle signaling, endoreduplication and aberrant cell cycle re-entry in diseases such as Alzheimer’s disease and prostate cancer.

Lab Website:

http://www.wisc.edu/agingresearch/research.htm

Selected Publications:

• Gallego, M.J., P. Porayette, M.M. Kaltcheva, S. Vadakkadath Meethal, and C.S. Atwood. 2009. Opioid and progesterone signaling is obligatory for early human embryogenesis. Stem Cells and Development. 18:737-740. [PDF]
• Simon, D., S. Vadakkadath Meethal, A.C. Wilson, M.J. Gallego, S.L. Weinecke, E. Bruce, P. Lyons, R.J. Haasl, R.L. Bowen, and C.S. Atwood. 2009. Activin receptor signaling regulates prostatic epithelial cell adhesion and viability. Neoplasia. 11:365-376. [PDF]
• Vadakkadath Meethal, S., T. Liu, H. Chan, E. Ginsburg, A.C. Wilson, D.N. Gray, R.L. Bowen, B.K. Vonderhaar, and C.S. Atwood. 2009. Identification of a regulatory loop for the synthesis of neurosteroids: A StAR-dependent mechanism involving HPG axis receptors. J. Neurochem. 110:1014-1027. [PDF]
• Porayette, P., M.J. Gallego, M.M. Kaltcheva, R.L. Bowen, S. Vadakkadath Meethal, and C.S. Atwood. 2009. Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells. J. Biol. Chem. Jun 19. [Epub ahead of print] [PDF]
• Gallego, M.J., P. Porayette, M.M. Kaltcheva, S. Vadakkadath Meethal, and C.S. Atwood. 2008. Opioid and progesterone signaling is obligatory for early human embryogenesis. Stem Cells and Development. [Epub ahead of print].
• Haasl, R.J., M. Reza Ahmadi, S. Vadakkadath Meethal, C.E. Gleason, S.C. Johnson, S. Asthana, R.L. Bowen, and C.S. Atwood. 2008. A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer’s disease in males carrying an apolipoprotein E epsilon4 Allele. BMC Medical Genetics 9:37. [PDF]
• Wilson, A.C., L. Clemente, T. Liu, R.L. Bowen, S. Vadakkadath Meethal, and C.S. Atwood. 2008. Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochimica et Biophysica Acta 1782:401-407. [PDF]
• Liu, T., J. Wimalasena, R.L. Bowen, and C.S. Atwood. 2007. Luteinizing hormone receptor mediates neuronal pregnenolone production via upregulation of steroidogenic acute regulatory protein expression. Journal of Neurochemistry 100:1329-1339. [PDF]
• Wilson, A.C., S. Salamat, R.J. Haasl, K.M. Roche, A. Karande, S. Vadakkadath Meethal, E. Terasawa, R.L. Bowen, and C.S. Atwood. 2006. Human extra-pituitary neurons possess GnRH I receptors that respond to GnRH by expressing luteinizing hormone. Journal of Endocrinology 191:651-665. [PDF]
• Bowen, R.L. and C.S. Atwood. 2004. Living and Dying for Sex: A theory of aging based on the modulation of cell cycle signaling by reproductive hormones. Gerontology 50:265-290.
• Bowen, R.L., G. Verdile, T. Liu, G. Perry, M.A. Smith, R.N. Martins, and C.S. Atwood. 2004. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-ß protein precursor and amyloid-ß deposition. Journal of Biological Chemistry 279:20539-45. [PDF]