Background: Frontotemporal dementia (FTD) is a neurodegenerative disease, resulting in progressive problems in language and/or behaviour and is often diagnosed before 65 years of age. Ubiquitin positive protein aggregates in the brain are among the key pathologic hallmarks of frontotemporal lobar degeneration (FTLD) postmortem. The TANK-binding kinase 1 gene (TBK1) is on the list of genes that can contribute to the development of FTD as well as the related neurodegenerative disease amyotrophic lateral sclerosis (ALS).
View Article and Find Full Text PDFWe identified an autosomal dominant progranulin mutation carrier without symptoms of dementia in her lifetime (Reduced Penetrance Mutation Carrier, RedPenMC). This resistance to develop expected pathology presents a unique opportunity to interrogate neurodegenerative mechanisms. We performed multimodal single-nuclei analyses of post-mortem frontal cortex from RedPenMC, including transcriptomics and global levels of chromatin marks.
View Article and Find Full Text PDFBackground And Objective: PSEN1-H163Y carriers, at the presymptomatic stage, have reduced FDG-PET binding in the cerebrum of the brain (Scholl et al., Neurobiol Aging 32:1388-1399, 2011). This could imply dysfunctional energy metabolism in the brain.
View Article and Find Full Text PDFBy covalently conjugating to target proteins, ubiquitin-like modifiers (UBLs) act as important regulators of target protein localization and activity, thereby playing a critical role in the orchestration of cellular biology. The most ancient and one of the least studied UBLs is Urm1, a dual-function protein that in parallel to performing similar functions as its prokaryotic ancestors in tRNA modification, also has adopted the capacity to conjugate to cellular proteins analogous to ubiquitin and other UBL modifiers. In order to increase the understanding of Urm1 and its role in multicellular organisms, we have used affinity purification followed by mass spectrometry to identify putative targets of Urm1 conjugation (urmylation) at three developmental stages of the Drosophila melanogaster lifecycle.
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