Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation. / Pircs, Karolina; Petri, Rebecca; Madsen, Sofia; Brattås, Per Ludvik; Vuono, Romina; Ottosson, Daniella R.; St-Amour, Isabelle; Hersbach, Bob A.; Matusiak-Brückner, Monika; Lundh, Sofia Hult; Petersén, Åsa; Déglon, Nicole; Hébert, Sébastien S.; Parmar, Malin; Barker, Roger A.; Jakobsson, Johan.

I: Cell Reports, Vol. 24, Nr. 6, 08.2018, s. 1397-1406.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Pircs, K, Petri, R, Madsen, S, Brattås, PL, Vuono, R, Ottosson, DR, St-Amour, I, Hersbach, BA, Matusiak-Brückner, M, Lundh, SH, Petersén, Å, Déglon, N, Hébert, SS, Parmar, M, Barker, RA & Jakobsson, J 2018, 'Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation', Cell Reports, vol. 24, nr. 6, s. 1397-1406. https://doi.org/10.1016/j.celrep.2018.07.017

APA

CBE

MLA

Vancouver

Author

Pircs, Karolina ; Petri, Rebecca ; Madsen, Sofia ; Brattås, Per Ludvik ; Vuono, Romina ; Ottosson, Daniella R. ; St-Amour, Isabelle ; Hersbach, Bob A. ; Matusiak-Brückner, Monika ; Lundh, Sofia Hult ; Petersén, Åsa ; Déglon, Nicole ; Hébert, Sébastien S. ; Parmar, Malin ; Barker, Roger A. ; Jakobsson, Johan. / Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation. I: Cell Reports. 2018 ; Vol. 24, Nr. 6. s. 1397-1406.

RIS

TY - JOUR

T1 - Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation

AU - Pircs, Karolina

AU - Petri, Rebecca

AU - Madsen, Sofia

AU - Brattås, Per Ludvik

AU - Vuono, Romina

AU - Ottosson, Daniella R.

AU - St-Amour, Isabelle

AU - Hersbach, Bob A.

AU - Matusiak-Brückner, Monika

AU - Lundh, Sofia Hult

AU - Petersén, Åsa

AU - Déglon, Nicole

AU - Hébert, Sébastien S.

AU - Parmar, Malin

AU - Barker, Roger A.

AU - Jakobsson, Johan

PY - 2018/8

Y1 - 2018/8

N2 - Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates, resulting in alterations in autophagy. However, the consequences of impaired autophagy for neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation as well as post-mortem material from patients with Huntington's disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNA-induced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together, these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation but also directly contributes to global alterations of intracellular post-transcriptional networks. Pircs et al. report that aggregation of the mutant huntingtin protein, a hallmark of Huntington's disease proteinopathy, impairs macroautophagy, leading to Argonaute-2 accumulation and global dysregulation of microRNAs. These results indicate that autophagy not only influences protein aggregation but also directly contributes to the global alterations of post-transcriptional networks in Huntington's disease.

AB - Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates, resulting in alterations in autophagy. However, the consequences of impaired autophagy for neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation as well as post-mortem material from patients with Huntington's disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNA-induced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together, these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation but also directly contributes to global alterations of intracellular post-transcriptional networks. Pircs et al. report that aggregation of the mutant huntingtin protein, a hallmark of Huntington's disease proteinopathy, impairs macroautophagy, leading to Argonaute-2 accumulation and global dysregulation of microRNAs. These results indicate that autophagy not only influences protein aggregation but also directly contributes to the global alterations of post-transcriptional networks in Huntington's disease.

KW - Argonaute-2

KW - autophagy

KW - Huntington's disease

KW - microRNA

KW - protein aggregation

U2 - 10.1016/j.celrep.2018.07.017

DO - 10.1016/j.celrep.2018.07.017

M3 - Article

VL - 24

SP - 1397

EP - 1406

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -