Transforming Growth Factor ßs (TGFßs) regulate the formation of the extracellular matrix and the growth and differentiation of various cell types in different organs. Latent TGFß Binding Proteins (LTBPs) are needed for secretion, correct folding and matrix deposition of TGFßs. In the brain, TGFß1 is inducible by ischemia, while ß2 and ß3 are present constitutively in several regions. Strong evidence indicates that TGFß1 has neuroprotective functions. The role and the distribution of LTBPs in the brain are unknown. We assume that the four known members of LTBPs also play a role in the processing of TGFßs in the nervous system. Preliminary in situ hybridisation studies clearly show that LTBPs are present in the rat brain.
High LTBP1 expression levels are seen in the medial preoptic area, the anteromedial thalamus and some cortical regions. LTBP2, an exceptional member of the LTBP protein family (no binding to TGFßs) is expressed only in cortical areas, hippocampus, and the perifornical/dorsolateral hypothalamus. LTBP3 exhibits a wider expression profile with the strongest expression in the ventral pallidum, anterodorsal and reticular thalamic nuclei, hippocampus, cortex, red nucleus and the periaqueductal gray.
The objective of the application is to initiate a research project on the distribution and function of LTBPs in the brain based on these new preliminary data and my background in histology and molecular biology. Apart from identifying the cells and brain regions that express LTBP-s in rat and human the role of this protein family in endogenous neuroprotective mechanisms will also be investigated using experimental ischemia models in rodents as well as post mortem brain samples of stroke patients. Altogether, this application can provide the foundation for a long-term investigation of TGFßs in the nervous systems and also for the applicant’s reintegration to the European and Hungarian neuroscience as an independent investigator.
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