Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0002736 (
amyotrophic lateral sclerosis
)
19,048
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations in the gene encoding fused in sarcoma (FUS) are linked to
amyotrophic lateral sclerosis
(
ALS
), but the mechanisms by which these mutants trigger neurodegeneration remain unknown. Endoplasmic reticulum (ER) stress is increasingly recognized as an important and early pathway to motor neuron death in
ALS
. FUS is normally located in the nucleus but in
ALS
, FUS redistributes to the cytoplasm and forms inclusions. In this study, we investigated whether FUS induces ER stress in a motor neuron like cell line (NSC-34). We demonstrate that ER stress is triggered in cells expressing mutant FUS, and this is closely associated with redistribution of mutant FUS to the cytoplasm. Mutant FUS also colocalized with
protein disulfide-isomerase
(
PDI
), an important ER chaperone, in NSC-34 cells and
PDI
was colocalized with FUS inclusions in human
ALS
lumbar spinal cords, in both sporadic
ALS
and mutant FUS-linked familial
ALS
tissues. These findings implicate ER stress in the pathophysiology of FUS, and provide evidence for common pathogenic pathways in
ALS
linked to the ER.
...
PMID:Mutant FUS induces endoplasmic reticulum stress in amyotrophic lateral sclerosis and interacts with protein disulfide-isomerase. 2245 2
