Research Roundup: see our neuroscience products in action
Our antibodies are used in cutting-edge neuroscience research around the world. Let's take a look at three recent studies showing our antibodies in action.
Today we focus on ER-mitochondria signaling in post-mortem Alzheimer's disease brain, novel autoantibodies from the serum of patients with melanoma-associated retinopathy, and proteins causing neurodevelopmental disorders.
1) Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer's disease brain (Lau et al. 2020)
Organelle-organelle communication between the endoplasmic reticulum (ER) and mitochondria is critical in organelle signaling. Many of the functions regulated by ER-mitochondria signaling are disrupted in cell and transgenic models of Alzheimer's disease. However, there is little evidence that ER-mitochondria signaling is altered in human Alzheimer's disease brains.
In this study, the authors looked at the ER-mitochondria tethering proteins VAPB and PTPIP51 in post mortem human Alzheimer's disease brains. The VAPB-PTPIP51 tethers are now known to regulate several ER-mitochondria signaling functions.
They found that VAPB and PTPIP51 are reduced in late-stage Alzheimer's disease in the cortex but not the cerebellum. In addition, a correlation was seen between the loss of VABP in the temporal cortex and the reductions in PTPI51, revealing a novel pathological feature in Alzheimer's disease.
Figure 1. Representative image of VAPB-PTPIP51 PLAs in pyramidal cells of control (left), Braak stage III-IV (middle), and Braak stage VI (right) Alzheimer's disease brains. Compared to controls, the VAPB-PTPIP51 interaction is reduced in temporal cortex pyramidal neurons in Braak stage III-IV (middle) but not Braak stage VI (right) Alzheimer's disease. The top panel shows low magnification, and the bottom panel shows a zoom of the boxed area at higher magnification. The graph shows the mean number of VAPB-PTPIP51 PLA signals per pyramidal neuron for each case. Image from Lau et al., 2020.
2) Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy (Varin et al. 2020)
Melanoma-associated retinopathy (MAR) is a rare paraneoplastic autoimmune retinal disorder usually occurring with metastatic melanoma. MAR is characterized by the production of autoantibodies targeting retinal proteins, particularly against TRPM1. This study demonstrates that patients presenting different anti-TRPM1 autoantibodies react to the three isoforms of TRPM1 with variable binding affinity.
The results suggest that a combination of different methods should be used to test for the presence of anti-TRPM1 autoantibodies in the sera of MAR patients.
- This study used our polyclonal anti-TRPM1 (HPA014779) antibody in ICC-IF and WB.
Figure 2. Immunolocalization studies using the MAR sera and anti-TRPM1 antibody in COS-7 cells overexpressing the three isoforms of TRPM1. (A) MAR1 (red) staining colocalized (yellow, merge) with TRPM1 (green) staining in COS-7 overexpressing all three isoforms of TRPM1. (B) MAR2 (red) staining colocalized (yellow, merge) with TRPM1 (green) staining in COS-7 overexpressing all three isoforms of TRPM1. (C) MAR3 (red) staining colocalized (yellow, merge) with TRPM1 (green) staining only in COS-7 overexpressing the 92+TRPM1 and the 109+TRPM1 isoform. Cells stained with rabbit polyclonal anti-TRPM1 (HPA014785). Image from Varin J. et al., 2020.
3) Loss of PHF6 leads to aberrant development of human neuron-like cells (Fliedner et al. 2020)
Pathogenic variants in PHF6 cause the X-linked neurodevelopmental disorder Borjeson–Forssman–Lehmann syndrome (BFLS). In this study, the authors found evidence that de novo variants occurring in females are more severe and result in loss of PHF6, contributing to the different phenotypes in male versus female individuals. In addition, knockout of PHF6 in neuron-like cells were examined to study related consequences of PHF6 loss.
The authors could demonstrate that intact PHF6 is necessary for proper neuron proliferation, neurite outgrowth, and migration. Impairment of these processes could contribute to the neurodevelopmental and cognitive dysfunction in BFLS.
This study used our polyclonal anti-PHF6 antibody (HPA001023) in immunofluorescence.
Figure 3. Immunofluorescence of fibroblasts of three individuals and one control. The three individuals have either a duplication of exons 4 and 5 (dup 4,5), a missense variant c.914G>T (p.(Cys305Phe), or a truncating variant c.955C>T (p.(Arg319*). In control, PHF6 expression could be observed in all fibroblast cells. In affected individuals, expression of PHF6 was present in 50% of cells. Scale bar represents 20 µm. Cells stained with rabbit polyclonal anti-PHF6 antibody (HPA001023). Image from Fliedner et al., 2020.
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1. Lau DHW, Paillusson S, Hartopp N, et al. Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer's disease brain. Neurobiol Dis. 2020;143:105020. doi:10.1016/j.nbd.2020.105020
2. Varin J, Reynolds MM, Bouzidi N, Tick S, Wohlschlegel J, Becquart O, et al. Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy. PLoS ONE 2020;15(4): e0231750.