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Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency A Randomized Clinical Trial KU Leuven
IMPORTANCE: Histone deacetylase inhibitors have been repeatedly shown to elevate progranulin levels in preclinical models. This report describes the first randomized clinical trial of a histone deacetylase inhibitor in frontotemporal dementia (FTD) resulting from progranulin (GRN) gene variations. OBJECTIVE: To characterize the safety, tolerability, plasma pharmacokinetics, and pharmacodynamic effects of oral FRM-0334 on plasma progranulin and ...
Peripheral progranulin levels do not reflect brain progranulin levels KU Leuven
© 2014 Future Medicine Ltd. EVALUATION OF: Nicholson AM, Finch NA, Thomas CS et al. Progranulin protein levels are differently regulated in plasma and CSF. Neurology 82(21), 1871-1878 (2014). Nicholson et al. report the first population-based comparative study of progranulin (GRN) levels in plasma and cerebrospinal fluid (CSF) in a large human cohort. Age, sex and rs5848 were found to be important modifiers of GRN levels in both plasma and CSF. ...
Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members Universiteit Antwerpen
Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)-positive pathology. The clinical presentation associated with GRN mutations is heterogeneous and may include clinical probable Alzheimers disease. All GRN mutations identified thus far cause disease through a uniform disease mechanism, i.e. the loss of functional GRN or ...
Progranulin variability has no major role in Parkinson disease genetic etiology Vrije Universiteit Brussel
Promoter DNA methylation regulates progranulin expression and is altered in FTLD Vrije Universiteit Brussel Universiteit Antwerpen
BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of neurodegenerative diseases associated with personality changes and progressive dementia. Loss-of-function mutations in the growth factor progranulin (GRN) cause autosomal dominant FTLD, but so far the pathomechanism of sporadic FTLD is unclear.
RESULTS: We analyzed whether DNA methylation in the GRN core promoter restricts GRN expression and, thus, might ...
Biological effects of progranulin in axonal regeneration and FTD KU Leuven
Loss of function mutations in progranulin (GRN) cause frontotemporal dementia, but how GRN haploinsufficiency causes neuronal dysfunction remains unclear. We previously showed that GRN is neurotrophic in vitro. Here, we used an in vivo axonal outgrowth system and observed a delayed recovery in GRN-/- mice after facial nerve injury. This deficit was rescued by reintroduction of human GRN and relied on its C-terminus and on neuronal GRN ...
Interplay between Progranulin and TDP-43 in the pathogenesis of Amyotrophic Lateral Sclerosis KU Leuven
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) are two related neurodegenerative disorders, representing the ends of a disease spectrum, with many intermediate forms in between. Not only clinically, but also at the genetic and pathological level, there is growing evidence for an overlap. TDP-43 has a central position in the pathogenesis: TDP-43 pathology is found in more than 95% of ALS patients (both in ...