The cytoplasmic mislocalization of otherwise predominantly nuclear RNA binding proteins, TDP-43 and FUS, implies a perturbation of the nucleocytoplasmic shuttling as a possible event in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Compromised nucleocytoplasmic shuttling has recently also been associated with a hexanucleotide repeat expansion mutation in C9orf72, which is the most common genetic cause of ALS and FTLD and leads to accumulation of cytoplasmic TDP-43 inclusions. Mutation in C9orf72 may disrupt nucleocytoplasmic shuttling on the level of C9ORF72 protein, the transcribed hexanucleotide repeat RNA, and/or dipeptide repeat proteins translated from the hexanucleotide repeat RNA. The defects of nucleocytoplasmic shuttling as disease mechanisms are discussed in this review in detail.
COBISS.SI-ID: 3106220
As members of the international consortium Project MinE, we have discovered and reported a new gene associated with an increased risk of ALS. The gene, C21 orf2, is very interesting for future studies that may bring increased understanding of the disease and novel therapies. To date, this was the biggest genome-wide association study and involved researchers and ALS associations from 15 countries.
COBISS.SI-ID: 29663527
This article provides an overview of allergen mimotopes identified through the phage display technique. We discuss the contribution of phage display peptide libraries in determining dominant B-cell epitopes of allergens, in developing mimotope immunotherapy, in understanding cross-reactivity, and in determining IgE epitope profiles of individual patients to improve diagnostics and individualize immunotherapy. We also discuss the advantages and pitfalls of the methodology used to identify and validate the mimotopes.
COBISS.SI-ID: 4144497
Potent, selective and reversible human BChE inhibitors were developed. The solved crystal structure of human BChE in complex with the most potent inhibitor reveals its binding mode and provides the molecular basis of its low nanomolar potency. Additionally, this compound is noncytotoxic and has neuroprotective properties. Furthermore, this inhibitor moderately crosses the blood-brain barrier and improves memory, cognitive functions and learning abilities of mice in a model of the cholinergic deficit that characterizes AD, without producing acute cholinergic adverse effects. Our study provides an advanced lead compound for developing drugs for alleviating symptoms caused by cholinergic hypofunction in advanced AD.
COBISS.SI-ID: 4263537
Organometalled compounds, including ruthenium, gained a lot of attention as anticancer agents. In this paper we report on clioquinol-ruthenium complex [Ru(eta6-p-cymene)(Cq)Cl] as a potent inhibitor of cathepsin B, a lysosomal cysteine peptidase, involved in tumour cell invasion and metastasis. Clioquinol-ruthenium complex did not exhibit cytotoxic effects it did, however, significantly reduced their ability for extracellular matrix degradation and invasiveness in two independent cell-based models.
COBISS.SI-ID: 4164977