• Nelson, Jay (PI)
  • Fujinami, Robert (PI)
  • Southern, Peter (PI)
  • Lampert, Peter (PI)
  • Criado, Jose (PI)
  • Williamson, R. Anthony (PI)
  • Burton, Dennis R. (PI)
  • Von Herrath, Matthias G. (PI)
  • Cooper, Neil (PI)
  • Wilson, Curtis (PI)
  • Mucke, Lennart (PI)
  • De La Torre, Juan C. (PI)
  • Whitton, J. Lindsay (PI)
  • Oldstone, Michael (PI)

Project: Research project

Project Details


This Program Project grant brings together molecular biologists,
virologists, immunologists, and experimental biologists to study
neurodegenerative, endocrine and renal disorders of aging using
transgenic models. The purpose is to understand pathogenesis and to
develop therapeutic approaches to treat such disorders. Two interlocking
hypotheses are addressed. The first is that expression of amyloid
protein, its precursor or mutant proteins, prion or viral proteins in
specialized cells of the central nervous system (CNS) using CNS specific
promoters for expression in astrocytes or neurons will provide models of
neurodegenerative disorders like Alzheimer's Disease. The second
hypothesis addresses the issue that environmental agents (viruses) cause
diseases in the aging population. It is proposed that acute or
persistent infection can cause degenerative progressive diseases of
endocrine cells, immunocompetent (lymphocytes) cells, neurons, or cells
of the renal glomeruli and tubules. Such diseases; i.e.,
neurodegenerative, diabetes, glomerulosclerosis, etc., can occur through
the ability of a virus to persist in specialized cells (i.e., islets of
Langerhans, lymphocytes, neurons, etc.) and turn down such cells
differentiation or luxury function (i.e., hormones, cytokines,
neurotransmitters, etc.). Such viruses need be non-cytolytic and hence
disease occurs by altering a cell's physiologic function in the absence
of the cell's destruction. Because virus induced disease can occur in
the absence of tissue injury many illnesses not previously thought to be
infectious in origin may be so. Studies of this hypothesis utilize
investigation of replication of a non-cytolytic virus in differentiated
cells in vitro and in vivo as well as transgenic technology to express
viral genes in specialized cells using the insulin promotor (beta cells
of the islets of Langerhans), GFAP promoter astrocytes) and NSE promoter
(neurons). In such instances cell and tissue injury and disease may
occur through the expression of the viral gene itself or through the
formation and action of antiself (antiviral) cytotoxic T lymphocytes or
antibodies following infection or immunization with the homologous or
closely related virus (cross-reactive immune response against self)
through a process we term molecular mimicry.
Effective start/end date8/1/8311/30/09


  • National Institutes of Health


  • Medicine(all)


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