The multifunctional nature of transforming growth factor-beta (TGF- beta) underlies its involvement in many pathologies, including neurodegenerative diseases. Changes that may occur in the expression of protein and mRNA for TGF-beta isoforms and signalling molecules in response to various disease states and tissue treatments are being investigated using immunohistochemistry and RT-PCR techniques. There is increased expression of TGF-beta2 in astrocytes in brains from patients with familial and sporadic Alzheimers disease (AD) when compared to controls. There is also expression of TGF-beta2 in neurons exhibiting neurofibrillary tangles (NFT). This increased expression is also found in eight other neurodegenerative diseases. It also appears that there is a loss of TGF-beta receptor expression in neurons exhibiting (NFTs). In primary cultures of rat embryo hippocampal neurons and in hNT cells (a terminally differentiated human cell line) TGF-betas can protect against the damaging effects of treatment with beta-amyloid peptide (beta-AP). TGF-beta treatment before addition of beta-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. Treatment of cells with beta-AP generates reactive oxygen species (ROS) which can damage the cells. Our studies show that TGF- beta protects neurons and neuroblastoma cell lines from damage caused by several types of ROS. Addition of TGF-beta increases the rate of oxygen consumption and total cellular ATP levels suggsting that its protective effects may be due to its ability to increase mitochondrial function and cellular energetics. We are also examining effects of TGF- beta on the activities of oxidative and antioxidative enzymes. - Alzheimer's disease, Cytotoxicity, immunohistochemistry, mitochondria, neuropathology, neuroprotection, Reactive oxygen species, transforming growth factor, - Neither Human Subjects nor Human Tissues
| Ren, R F; Lah, J J; Diehlmann, A et al. (1999) Differential effects of transforming growth factor-beta(s) and glial cell line-derived neurotrophic factor on gene expression of presenilin-1 in human post-mitotic neurons and astrocytes. Neuroscience 93:1041-9 |
