Susan Bektesh

Bio: Susan Bektesh is an academic researcher from Amgen. The author has contributed to research in topics: Neurotrophic factors & Glial cell line-derived neurotrophic factor. The author has an hindex of 5, co-authored 8 publications receiving 3575 citations.

GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons

Abstract: A potent neurotrophic factor that enhances survival of midbrain dopaminergic neurons was purified and cloned. Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer that is a distantly related member of the transforming growth factor-beta superfamily. In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake. These effects were relatively specific; GDNF did not increase total neuron or astrocyte numbers nor did it increase transmitter uptake by gamma-aminobutyric-containing and serotonergic neurons. GDNF may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons.

Glial derived neurotrophic factor

Abstract: A novel neurotrophic factor referred to as glial derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

Production of biologically active, recombinant members of the NGF/BDNF family of neurotrophic proteins

Abstract: This invention describes processes for producing mature human members of the NGF/BDNF family of neurotrophic proteins that are fully biologically active. In addition, the gene encoding human BDNF and human BDNFare disclosed. A previously-unreported member of the NGF/BDNFfamily of neurotrophic proteins, NGF-3, has been identified and a portion of the gene encoding for the NGF-3 has been described.

TGF-beta signal transduction.

Abstract: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms.

Abstract: In the last 10 years, a large family of secreted signaling molecules has been discovered that appear to mediate many key events in normal growth and development. The family is known as the TGF-p superfamily (Massague 1990), a name taken from the first member of the family to be isolated (transforming growth factor-^l). This name is somewhat misleading, because TGF-p 1 has a large number of effects in different systems (Spom and Roberts 1992). It actually inhibits the proliferation of many different cell lines, and its original "transforming" activity may be due to secondary effects on matrix pro­ duction and synthesis of other growth factors (Moses et al. 1990). The two dozen other members of the TGF-p superfamily have a remarkable range of activities. In Diosophila, a TGF-p-related gene is required for dorsoventral axis formation in early embryos, communication between tissue layers in gut development, and correct proximal distal patterning of adult appendages. In Xenopus, a TGF-p-related gene is expressed specifically at one end of fertilized eggs and may function in early signaling events that lay out the basic body plan. In mammals, TGF-p-related molecules have been found that control sexual development, pituitary hormone production, and the creation of bones and cartilage. The recognition of TGF-p superfamily members in many different organ­ isms and contexts provides one of the major unifying themes in recent molecular studies of animal growth and development. The rough outlines of the TGF-p family were first rec­ ognized in the 1980s. Since that time, a number of ex­ cellent reviews have appeared that summarize the prop­ erties of different family members (Ying 1989; Massague 1990; Lyons et al. 1991; Spom and Roberts 1992). Here, I will focus on four areas that have seen major progress in the last 3 years: structural characterization of the signal­ ing molecule, isolation of new family members, cloning of receptor molecules, and new genetic tests of the func­ tions of these factors in different organisms.

Neuroinflammation in Parkinson's disease: a target for neuroprotection?

Abstract: Parkinson's disease is characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the cause of the neuronal loss in Parkinson's disease is poorly understood. Neuroinflammatory mechanisms might contribute to the cascade of events leading to neuronal degeneration. In this Review, we describe the evidence for neuroinflammatory processes from post-mortem and in vivo studies in Parkinson's disease. We further identify the cellular and molecular events associated with neuroinflammation that are involved in the degeneration of dopaminergic neurons in animal models of the disease. Overall, available data support the importance of non-cell-autonomous pathological mechanisms in Parkinson's disease, which are mostly mediated by activated glial and peripheral immune cells. This cellular response to neurodegeneration triggers deleterious events (eg, oxidative stress and cytokine-receptor-mediated apoptosis), which might eventually lead to dopaminergic cell death and hence disease progression. Finally, we highlight possible therapeutic strategies (including immunomodulatory drugs and therapeutic immunisation) aimed at downregulating these inflammatory processes that might be important to slow the progression of Parkinson's disease.