Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Aβ) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Aβ directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Aβ-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Aβ amino acids 26-42. Interestingly, intracellular Aβ binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Aβ in the development of ALS by interacting with the SOD1 G93A mutant.
| Original language | English |
|---|---|
| Pages (from-to) | 611-617 |
| Number of pages | 7 |
| Journal | Experimental and Molecular Medicine |
| Volume | 41 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2009 Sep 30 |
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Keywords
- Alzheimer disease
- Amyloid β-protein
- Amyotrophic lateral sclerosis
- Enzymology
- Protein interaction domains and motifs
- Superoxide dismutase 1
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Molecular Medicine
- Clinical Biochemistry
Cite this
Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1 : Implications for the pathogenesis of amyotrophic lateral sclerosis. / Eun, Jin Yoon; Park, Hyo Jin; Kim, Goo Young; Cho, Hyungmin; Choi, Jung Ha; Park, Hye Yoon; Jang, Ja Young; Rhim, Hyangshuk; Kang, Seong Man.
In: Experimental and Molecular Medicine, Vol. 41, No. 9, 30.09.2009, p. 611-617.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1
T2 - Implications for the pathogenesis of amyotrophic lateral sclerosis
AU - Eun, Jin Yoon
AU - Park, Hyo Jin
AU - Kim, Goo Young
AU - Cho, Hyungmin
AU - Choi, Jung Ha
AU - Park, Hye Yoon
AU - Jang, Ja Young
AU - Rhim, Hyangshuk
AU - Kang, Seong Man
PY - 2009/9/30
Y1 - 2009/9/30
N2 - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Aβ) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Aβ directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Aβ-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Aβ amino acids 26-42. Interestingly, intracellular Aβ binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Aβ in the development of ALS by interacting with the SOD1 G93A mutant.
AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Aβ) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Aβ directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Aβ-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Aβ amino acids 26-42. Interestingly, intracellular Aβ binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Aβ in the development of ALS by interacting with the SOD1 G93A mutant.
KW - Alzheimer disease
KW - Amyloid β-protein
KW - Amyotrophic lateral sclerosis
KW - Enzymology
KW - Protein interaction domains and motifs
KW - Superoxide dismutase 1
UR - http://www.scopus.com/inward/record.url?scp=70349449750&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349449750&partnerID=8YFLogxK
U2 - 10.3858/emm.2009.41.9.067
DO - 10.3858/emm.2009.41.9.067
M3 - Article
C2 - 19478559
AN - SCOPUS:70349449750
VL - 41
SP - 611
EP - 617
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
SN - 1226-3613
IS - 9
ER -