Rostalski, H., Leskelä, S., Huber, N., Katisko, K., Cajanus, A., Solje, E., … Haapasalo, A. (2019). Astrocytes and Microglia as Potential Contributors to the Pathogenesis of C9orf72 Repeat Expansion-Associated FTLD and ALS. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.00486
Astrocytes and microglia as potential contributors to the pathogenesis of C9orf72 repeat expansion-associated FTLD and ALS
|Author:||Rostalski, Hannah1; Leskelä, Stina1; Huber, Nadine1;|
1A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
2Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland
3Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland
4Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
5Medical Research Center, Oulu University Hospital, Oulu, Finland
6Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 2.1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019092629850
|Publish Date:|| 2019-09-26
Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases with a complex, but often overlapping, genetic and pathobiological background and thus they are considered to form a disease spectrum. Although neurons are the principal cells affected in FTLD and ALS, increasing amount of evidence has recently proposed that other central nervous system-resident cells, including microglia and astrocytes, may also play roles in neurodegeneration in these diseases. Therefore, deciphering the mechanisms underlying the disease pathogenesis in different types of brain cells is fundamental in order to understand the etiology of these disorders. The major genetic cause of FTLD and ALS is a hexanucleotide repeat expansion (HRE) in the intronic region of the C9orf72 gene. In neurons, specific pathological hallmarks, including decreased expression of the C9orf72 RNA and proteins and generation of toxic RNA and protein species, and their downstream effects have been linked to C9orf72 HRE-associated FTLD and ALS. In contrast, it is still poorly known to which extent these pathological changes are presented in other brain cells. Here, we summarize the current literature on the potential role of astrocytes and microglia in C9orf72 HRE-linked FTLD and ALS and discuss their possible phenotypic alterations and neurotoxic mechanisms that may contribute to neurodegeneration in these diseases.
Frontiers in neuroscience
|Type of Publication:||
A2 Review article in a scientific journal
|Field of Science:||
3124 Neurology and psychiatry
This study was supported by grants fromthe Academy of Finland, grant nos. 315459 (AH), 315460 (AR), 288659 (TN), and 307866 (MH); Yrjö Jahnsson Foundation, grant no. 20187070 (AH); ALS tutkimuksen tuki ry. registered association (HR, SL, NH); Sigrid Jusélius Foundation (MH); Maire Taponen Foundation (AC); Finnish Cultural Foundation (AC); Finnish Brain Foundation (KK); Finnish Medical Foundation (KK); Päivikki and Sakari Sohlberg Foundation (KK); the Strategic Neuroscience Funding of the University of Eastern Finland (AH,MH); and Neurocenter Finland—AlzTrans pilot project (MH).
© 2019 Rostalski, Leskelä, Huber, Katisko, Cajanus, Solje, Marttinen, Natunen, Remes, Hiltunen and Haapasalo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.