Kurzfassung

Intellectual disability (ID) is characterized by significant limitations both in intellectual functioning and in adaptive behaviour, which covers many everyday social and practical skills (American Association on Intellectual and Developmental Disabilities). It can be caused by a diverse spectrum of factors including birth complications and gene mutations. During the last decade a number of genes has been identified that are involved in ID. Although at first sight these genes seem to be very...Intellectual disability (ID) is characterized by significant limitations both in intellectual functioning and in adaptive behaviour, which covers many everyday social and practical skills (American Association on Intellectual and Developmental Disabilities). It can be caused by a diverse spectrum of factors including birth complications and gene mutations. During the last decade a number of genes has been identified that are involved in ID. Although at first sight these genes seem to be very different in terms of their function within the brain and during the development of the brain and of intellectual capabilities, it turned out that mutation of one or the other of these genes affect the function of only a handful of molecules. These molecules form something like the common path in the pathogenesis of ID. Among them is the mammalian target of rapamycin (mTOR) kinase, which has been shown to play an important role in the uptake and processing of nerve cell stimulation. The ability of nerve cells to enhance stimuli on the basis of previous stimulations is called “long term potentiation (LTP)”. LTP is the basis of learning and memory.
In a number of mental disorders that are characterized by ID mTOR has been shown to be significantly disturbed, which leads to an impairment of LTP and which seems to be the molecular cause of deficits in learning and memory in patients. We have chosen three of these mental disorders, namely RTT syndrome (RTT), CDKL5 deficiency (CD) and Opitz/BBB/G syndrome (OS), to further study the relationship between mTOR deficiency, LTP impairment and cognitive dysfunction. In this project we will use cell culture models as well as animal models carrying the respective gene defects. In a close comparison of mTOR activity, LTP and cognitive behavior of animals we will try to identify those parts of ID that are caused by loss of mTOR function. A clear knowledge of cellular processes and molecules that are involved in ID will hopefully pave the way towards the identification of novel targets that can be used for the development of drug therapies for genetically caused ID.» weiterlesen» einklappen