There is a clear rationale for elucidating effective ways of identifying and treating disease-related malnutrition (DRM), given the physiological and financial consequences of this common condition and its treatability.Evidence indicates the efficacy of nutritional support methods (oral, tube and intravenous) in increasing total nutritional intake while having little effect on appetite, satiety, appetite mediators (e.g. When used as the only source of nutrition, artificial nutrition can effectively maintain nutritional intake, and yet many patients find enteral or parenteral feeding alone is unable to relieve distressing appetite sensations, and unusual temporal patterns (including dissociation between hunger and desire to eat) occur.
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However, while the molecules that regulate SV exo/endocytosis have been extensively studied, those that regulate SV maintenance and degradation remain almost entirely unknown.
The overall goal of this proposal is to elucidate the molecular pathway that mediates SV protein degradation in mammalian glutamatergic neurons.
We will again use techniques from Aim 1, together with Rab35 gain- and loss-of-function, to reveal whether Rab35 sorts SV membrane proteins into endosomal intermediates, promoting their entry into an ESCRT-dependent degradative pathway.
Together, these studies will provide novel insights into how SV-stasis is maintained, and how its dysregulation contributes to synapse degeneration and the etiology of neurodegenerative disease.Your access to the NCBI website at gov has been temporarily blocked due to a possible misuse/abuse situation involving your site.This is not an indication of a security issue such as a virus or attack.To test this hypothesis, we will use biochemistry, immunofluorescence microscopy, live imaging, and electron microscopy to assess effects of Siah1 gain- or loss-of-function on SV protein abundance and turnover.In Aim 2, we will determine whether ubiquitinated SV proteins are targeted to lysosomes via the ESCRT pathway.If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account.