| 1. |
- Ansell - Schultz, Anna, et al.
(författare)
-
Reduced retromer function results in the accumulation of amyloid-beta oligomers
- 2018
-
Ingår i: Molecular and Cellular Neuroscience. - : Academic Press. - 1044-7431 .- 1095-9327. ; 93, s. 18-26
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimers disease (AD) is a neurodegenerative disorder characterized by a progressive loss of multiple cognitive functions. Accumulation of amyloid beta oligomers (oA beta) play a major role in the neurotoxicity associated with the disease process. One of the early affected brain regions is the hippocampus, wherein a reduction of the vacuolar protein sorting-associated protein 35 (VPS35), the core protein comprising the retromer complex involved in cellular cargo sorting, has been identified. To investigate the role of the retromer function on the accumulation and clearance of oA beta, we reduced retromer function by selectively inhibiting VPS35 gene expression using siRNA in differentiated neuronal SH-SY5Y cells. As cell-to-cell transfer of oA beta to new brain regions is believed to be important for disease progression we investigated the effect of VPS35 reduction both in cells with direct uptake of oA beta and in cells receiving oA beta from donor cells. We demonstrate that reduced retromer function increases oA beta accumulation in both cell systems, both the number of cells containing intracellular oA beta and the amount within them. This effect was shown at different time points and regardless if the AD originated from the extracellular milieu or via a direct neuronal cell-to-cell transfer. Interestingly, not only did reduced VPS35 cause oA beta accumulation, but oA beta treatment alone also lead to a reduction of VPS35 protein content. The accumulated oA beta seems to co-localize with VPS35 and early endosome markers. Together, these findings provide evidence that reduced retromer function decreases the ability for neurons to transport and clear neurotoxic oA beta received through different routes resulting in the accumulation of oA beta. Thus, enhancing retromer function may be a potential therapeutic strategy to slow down the pathophysiology associated with the progression of AD.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Samuelsson, My, et al.
(författare)
-
Soluble plasma proteins ST2 and CD163 as early biomarkers of nephropathy in Swedish patients with diabetes, 15-34 years of age : a prospective cohort study
- 2017
-
Ingår i: Diabetology & Metabolic Syndrome. - : BIOMED CENTRAL LTD. - 1758-5996. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to investigate plasma levels of sST2 and sCD163 to determine whether they at an early stage could predict development of diabetic nephropathy and/or diabetic retinopathy in patients at clinical onset. Methods: Patients diagnosed with diabetes mellitus at age 15-34 years between 1987 and 1988 (n = 220) were included. Data such as BMI, smoking, HbA1c and islet cell antibodies were collected at time of diagnosis. Within the 10 year follow-up period, 112 patients (51%) developed following diabetes related complications; retinopathy (n = 91), nephropathy (n = 12) or both (n = 9). Plasma concentrations of sST2 and sCD163 were measured at time of diagnosis and levels compared between different complication groups. Results: Plasma levels of sST2 were significantly higher in patients who later developed nephropathy (n = 21; 1012 [773-1493] pg/ml) compared to those who did not (n = 199; 723 [449-1084] pg/ml; p = 0.006). A tendency for higher plasma levels of sCD163 was observed but not statistically significant (p = 0.058). Conclusions: sST2 and sCD163 show promise as potential biomarkers for the development of nephropathy already at clinical onset. sST2 and/or sCD163 could possibly be part of a biomarker panel aimed to find patients at high risk of developing nephropathy. Both markers need to be investigated in a larger prospective study.
|
|
