The multifunctional nature of transforming growth factor-b (TGF-b) underlies its involvement in many pathologies, including neurodegenerative diseases. Changes that may occur in the expression of protein and mRNA for TGF-b isoforms in response to various disease states and tissue treatments are being investigated using immunohistochemistry and RT-PCR techniques. There is increased expression of TGF-b2 in astrocytes in brains from patients with familial and sporadic Alzheimer's disease (AD) when compared to controls. There is also expression of TGF-b2 in neurons exhibiting neurofibrillary tangles. This increased expression is also found in eight other neurodegenerative diseases. We are now investigating changes in TGF-b receptor expression in AD. In primary cultures of rat embryo hippocampal neurons and in hNT cells (a terminally differentiated human cell line) TGF-bs can protect against the damaging effects of treatment with b- amyloid peptide b-AP. TGF-b treatment before addition of b-AP causes a two-to three-fold increase in cell survival. These protective effects are accompanied by increased expression of """"""""anti-apoptotic"""""""" genes such as Bcl-Xs and decreased expression of """"""""pro-apoptotic"""""""" genes such as Bax and Bcl-XL. Additionally, we are investigating the ability of TGF-b to alter expression of wild-type and mutant presenilins, the recently cloned genes that regulate processing and production of b-AP.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005550-11
Application #
6100821
Study Section
Special Emphasis Panel (LC)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code