Craig S. Atwood

 

 

Endocrinology of Alzheimer's Disease and Aging

E-mail: csa@medicine.wisc.edu

Research Strength: Neurobiology of Disease

Research in my laboratory is aimed at at identifying ways to delay the onset or slow the progression of age-related diseases like Alzheimer's disease (AD). In this connection, we have focussed heavily on understanding how hormones of the hypothalamic-pituitary-gonadal (HPG) axis regulate neuronal growth, differentiation/function and death. Menopause and andropause induce changes in the serum concentrations of HPG hormones that alter the processing of the amyloid-ß precursor protein, leading to an increase in amyloid-ß generation, the major component of amyloid plaques that deposit in the brains of individuals with AD. In addition, we have found that neurons in the senescent brain develop other phenotypic characteristics of dividing/transformed cells, such as the expression of luteinizing hormone and osteopontin. This research has been instrumental in the development of leuprolide acetate (a GnRH agonist) for the treatment of Alzheimer's disease (currently in Phase III clinical trials in the USA and Europe). This basic research also has led to the formulation of a new theory of aging - 'The Reproductive Cell Cycle Theory of Aging'. The basic premise behind this theory, and my laboratory, is that reproductive hormones act in an antagonistic pleiotrophic manner 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 (dyosis). Research in our laboratory continues to examine how reproduction regulates longevity at the biochemical, physiological and evolutionary levels using molecular, cellular and animal approaches. Recently, we discovered that the nematode C. elegans, an animal model of aging, has an evolutionarily conserved, functional, primordial chemo-neuro-endocrine sensory system that regulates reproduction. We are now using this new model system to study interactions between reproductive endocrinology and aging.

Lab Website:

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

Selected Publications:

• Liu, T., G. Perry, H.W. Chan, G. Verdile, R.N. Martins, M.A. Smith, and C.S. Atwood. 2004. Amyloid-ß-induced toxicity of primary neurons is dependent upon differentiation associated increases in tau and cyclin-dependent kinase 5. J. Neurochem. 88: 554-563.
• 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. J. Bio. Chem. 279: 20539-20545.
• 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.