RGD Reference Report - Effects of aluminium on ß-amyloid (1-42) and secretases (APP-cleaving enzymes) in rat brain. - Rat Genome Database

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Effects of aluminium on ß-amyloid (1-42) and secretases (APP-cleaving enzymes) in rat brain.

Authors: Wang, Linping  Hu, Jiali  Zhao, Yue  Lu, Xiaoting  Zhang, Qinli  Niu, Qiao 
Citation: Wang L, etal., Neurochem Res. 2014 Jul;39(7):1338-45. doi: 10.1007/s11064-014-1317-z. Epub 2014 May 3.
RGD ID: 13703037
Pubmed: PMID:24792732   (View Abstract at PubMed)
DOI: DOI:10.1007/s11064-014-1317-z   (Journal Full-text)

Chronic administration of aluminium has been proposed as an environmental factor that may affect some pathological changes related to neurotoxicity and Alzheimer's disease (AD). The abnormal generation and deposition of ß-amyloid (Aß) in senile plaques are hallmark features in the brains of AD patients. Furthermore, Aß is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or ß-secretase) and γ-secretase. In the present study, we investigated the modulation of Aß deposition and neurotoxicity in aluminium-maltolate-treated (0, 15, 30, 45 mmol/kg body weight via intraperitoneal injection) in experimental rats. We measured Aß1-40 and Aß1-42 in the cortex and hippocampus in rat brains using ELISA. Subtypes of α-secretase, ß-secretase, and γ-secretase, including ADAM9, ADAM10, ADAM17 (TACE), BACE1, presenilin 1 (PS1) and nicastrin (NCT), were determined using western blotting analyses. These results indicated that aluminium-maltolate induced an AD-like behavioural deficit in rats at 30 and 45 mmol/kg body weight. Moreover, the Aß1-42 content increased significantly, both in the cortex and hippocampus, although no changes were observed in Aß1-40. Furthermore, ADAM9, ADAM10, and ADAM17 decreased significantly; in contrast, BACE1, PS1, and NCT showed significant increase. Taken together, these results suggest that the changes in secretases may correlate to the abnormal deposition of Aß by aluminium in rat brains.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADAM10HumanAlzheimer's disease  ISOAdam10 (Rattus norvegicus)protein:decreased expression:cerebral cortex and hippocampusRGD 
ADAM17HumanAlzheimer's disease  ISOAdam17 (Rattus norvegicus)protein:decreased expression:cerebral cortex and hippocampusRGD 
ADAM9HumanAlzheimer's disease  ISOAdam9 (Rattus norvegicus)protein:decreased expression:hippocampusRGD 
Adam10RatAlzheimer's disease  IEP protein:decreased expression:cerebral cortex and hippocampusRGD 
Adam10MouseAlzheimer's disease  ISOAdam10 (Rattus norvegicus)protein:decreased expression:cerebral cortex and hippocampusRGD 
Adam17RatAlzheimer's disease  IEP protein:decreased expression:cerebral cortex and hippocampusRGD 
Adam17MouseAlzheimer's disease  ISOAdam17 (Rattus norvegicus)protein:decreased expression:cerebral cortex and hippocampusRGD 
Adam9RatAlzheimer's disease  IEP protein:decreased expression:hippocampusRGD 
Adam9MouseAlzheimer's disease  ISOAdam9 (Rattus norvegicus)protein:decreased expression:hippocampusRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adam10  (ADAM metallopeptidase domain 10)
Adam17  (ADAM metallopeptidase domain 17)
Adam9  (ADAM metallopeptidase domain 9)

Genes (Mus musculus)
Adam10  (a disintegrin and metallopeptidase domain 10)
Adam17  (a disintegrin and metallopeptidase domain 17)
Adam9  (ADAM metallopeptidase domain 9)

Genes (Homo sapiens)
ADAM10  (ADAM metallopeptidase domain 10)
ADAM17  (ADAM metallopeptidase domain 17)
ADAM9  (ADAM metallopeptidase domain 9)


Additional Information