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 in response to various disease states and tissue treatments are being investigated using immunohistochemistry and Northern blot techniques. For example, in Kaposi's sarcoma there is increased expression of TGF-beta1 in mononuclear cells, vascular smooth muscle cells, pericytes and spindle-shaped cells. There is increased expression of TGF-beta2 in astrocytes in brains from patients with familial and sporadic Alzheimer's disease (AD) when compared to controls. There is also expression of TGF-beta2 in amyloid plaques and neurons exhibiting neurofibrillary tangles. While there is more perineuronal expression of TGF-beta1 in controls than in AD patients, there is similar expression of TGF-beta3. Additionally, AD patients express inducible nitric oxide synthase protein more extensively than do controls. In primary neuronal cultures, TGF-betas can protect against the damaging effects of treatment with beta- amyloid peptide (beta-AP). TGF-beta treatment, either before or after addition of beta-AP, causes a two- to three-fold increase in cell survival. This may be one of the functions of increased immunoreactive TGF-beta seen in brains of AD patients. The ability of TGF-beta to affect phosphorylation of the protein tau, which contributes to the formation of neurofibrillary tangles, is also being investigated.
