Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion

Ber, Isabelle Le

doi:10.1016/j.neurol.2015.04.004

Cited by 7 publications

(1 citation statement)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many novel genes have been recently associated with ALS/FTLD [ 29 , 37 ]. Among these, hexanucleotide repeat expansion in the C9orf72 gene has been shown to be the main cause of ALS/FTLD [ 13 , 38 , 51 ], for which three disease mechanisms have been proposed: toxicity of RNA foci formed by RNA repeats, toxicity induced by dipeptide repeat aggregation as a result of repeat associated non-ATG mediated RNA translation (RAN), and reduced expression of the C9orf72 gene [ 26 , 39 ]. Recently, several animal models have been established to investigate repeat associated gain of toxicity [ 10 , 18 , 31 , 33 , 35 , 47 ] as well as the physiological functions of C9orf72 in mammals.…”

Section: Introductionmentioning

confidence: 99%

The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway

Sullivan

Zhou

Robins

et al. 2016

acta neuropathol commun

257

306

View full text Add to dashboard Cite

Hexanucleotide repeat expansion in the C9orf72 gene is a leading cause of frontotemporal lobar degeneration (FTLD) with amyotrophic lateral sclerosis (ALS). Reduced expression of C9orf72 has been proposed as a possible disease mechanism. However, the cellular function of C9orf72 remains to be characterized. Here we report the identification of two binding partners of C9orf72: SMCR8 and WDR41. We show that WDR41 interacts with the C9orf72/SMCR8 heterodimer and WDR41 is tightly associated with the Golgi complex. We further demonstrate that C9orf72/SMCR8/WDR41 associates with the FIP200/Ulk1 complex, which is essential for autophagy initiation. C9orf72 deficient mice, generated using the CRISPR/Cas9 system, show severe inflammation in multiple organs, including lymph node, spleen and liver. Lymph node enlargement and severe splenomegaly are accompanied with macrophage infiltration. Increased levels of autophagy and lysosomal proteins and autophagy defects were detected in both the spleen and liver of C9orf72 deficient mice, supporting an in vivo role of C9orf72 in regulating the autophagy/lysosome pathway. In summary, our study elucidates potential physiological functions of C9orf72 and disease mechanisms of ALS/FTLD.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0324-5) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway

Sullivan

Zhou

Robins

et al. 2016

acta neuropathol commun

257

306

View full text Add to dashboard Cite

show abstract

Expression and Distribution of Arylsulfatase B are Closely Associated with Neuron Death in SOD1 G93A Transgenic Mice

et al. 2017

View full text Add to dashboard Cite

The known proteins only explained the partial pathogenesis of amyotrophic lateral sclerosis (ALS). Therefore, this study aimed to search the novel proteins possibly involved in ALS. In this study, we analyzed the expression and distribution of the candidate protein arylsulfatase B (ARSB) in the different segments, anatomic regions, and neural cells of spinal cord at the different stages of the wild-type and [Cu/Zn] superoxide dismutase 1 (SOD1) G93A transgenic mice using the fluorescent immunohistochemistry and the western blot. The results revealed that the ARSB was extensively expressed and distributed in the entire spinal cord; the expression and distribution of ARSB was significantly different in the different regions of spinal cord, the anterior horn of gray matter (AHGM) was significantly more than that in the posterior horn of gray matter (PHGM) and significantly more than that in the central canal, and ARSB was mainly distributed in the microglia and neuron cells in the wild-type mice. The expression of ARSB significantly increased in other anatomic regions besides the thoracic PHGM, significantly decreased at the progression stage, occurred in the redistribution from the AHGM and the PHGM to the central canal at the onset and progression stages, and no any alteration of ARSB expression and distribution occurred between the different neural cells in the SOD1 G93A mice compared with the wild-type mice. The increase of ARSB expression and distribution followed with the increased of neuron death. Our data suggested that the abnormal expression and distribution of ARSB were closely associated with the neuron death in the SOD1 G93A transgenic mice.

show abstract

Diagnostic positif et étiologique des démences frontotemporales

Lebouvier

Bertoux

Leroy

et al. 2019

Pratique Neurologique - FMC

View full text Add to dashboard Cite

Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion

Cited by 7 publications

References 76 publications

The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway

The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway

Expression and Distribution of Arylsulfatase B are Closely Associated with Neuron Death in SOD1 G93A Transgenic Mice

Diagnostic positif et étiologique des démences frontotemporales

Contact Info

Product

Resources

About