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)
Mechanisms of human mutant superoxide dismutase 1 (SOD1)-induced toxicity in causing the familial form of
amyotrophic lateral sclerosis
(
ALS
) remain elusive. Identification of new proteins that can selectively interact with mutant SOD1s and investigation of their potential roles in
ALS
are important to discover new pathways that are involved in disease pathology. Using the yeast two-hybrid system, we identified the adaptor-associated kinase 1 (AAK1), a regulatory protein in clathrin-coated vesicle endocytic pathway that selectively interacted with the mutant but not the wild-type SOD1. Using both transgenic mouse and rat SOD1-linked familial
ALS
(FALS) models, we found that AAK1 was partially colocalized with the endosomal and presynaptic protein markers under the normal physiological condition, but was mislocated into aggregates that contained mutant SOD1s and the neurofilament proteins in rodent models of
ALS
in disease.
AAK1 protein
levels were also decreased in
ALS
patients. These results suggest that dysfunction of a component in the endosomal and synaptic vesicle recycling pathway is involved in
ALS
pathology.
...
PMID:Dysfunction of endocytic kinase AAK1 in ALS. 2551 44
