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Open Access 01-08-2016 | Review

Inside out: the role of nucleocytoplasmic transport in ALS and FTLD

Authors: Steven Boeynaems, Elke Bogaert, Philip Van Damme, Ludo Van Den Bosch

Published in: Acta Neuropathologica | Issue 2/2016

Abstract

Neurodegenerative diseases are characterized by the presence of protein inclusions with a different protein content depending on the type of disease. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are no exceptions to this common theme. In most ALS and FTLD cases, the predominant pathological species are RNA-binding proteins. Interestingly, these proteins are both depleted from their normal nuclear localization and aggregated in the cytoplasm. This key pathological feature has suggested a potential dual mechanism with both nuclear loss of function and cytoplasmic gain of function being at play. Yet, why and how this pathological cascade is initiated in most patients, and especially sporadic cases, is currently unresolved. Recent breakthroughs in C9orf72 ALS/FTLD disease models point at a pivotal role for the nuclear transport system in toxicity. To address whether defects in nuclear transport are indeed implicated in the disease, we reviewed two decades of ALS/FTLD literature and combined this with bioinformatic analyses. We find that both RNA-binding proteins and nuclear transport factors are key players in ALS/FTLD pathology. Moreover, our analyses suggest that disturbances in nucleocytoplasmic transport play a crucial initiating role in the disease, by bridging both nuclear loss and cytoplasmic gain of functions. These findings highlight this process as a novel and promising therapeutic target for ALS and FTLD.

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Title: Inside out: the role of nucleocytoplasmic transport in ALS and FTLD
Authors: Steven Boeynaems
Elke Bogaert
Philip Van Damme
Ludo Van Den Bosch
Publication date: 01-08-2016
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 2/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1586-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Inside out: the role of nucleocytoplasmic transport in ALS and FTLD

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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