Location

Jereld R. Nicholson Library

Subject Area

Biology

Description

The presence of Beta-Amyloid (Aβ) containing plaques in the brain is one of the histological hallmarks of Alzheimer’s Disease. β-secretase (BACE) is the enzyme responsible for producing this Aβ cleavage product and has also been shown to affect myelination and general neuronal activity. Observations from geriatric medicine suggest that there may be an increase in seizure activity associated with Alzheimer’s Disease. Preliminary data suggests that both over- and under-expression of BACE contributes to mechanically stimulated seizures in Drosophila. In vertebrates, seizure activity has been correlated with many factors including Neuregulin production and Na+ Pump activity. Both of these proteins have also been shown to require BACE activity for proper function. However, their roles in BACE related seizures remains unknown. Here we are following up on this preliminary study and exploring the roles of Vein (the Drosophila homolog of Neuregulin) and Numb (a negative regulator of the Notch Pathway). We have confirmed that any perturbation in dBACE (Drosophila BACE) levels causes a significant increase in age related seizures, suggesting that that BACE levels must be tightly regulated. In addition an increase of Vein levels also cause a dramatic increase in seizure amounts and duration suggesting that BACE, at least in part, is acting through this signaling pathway. Understanding which BACE related signaling pathways are responsible for age related seizure activity can lead to new treatments which will hopefully slow the progression of Alzheimer’s and other related neurodegenerative diseases.

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May 15th, 9:30 AM May 15th, 10:45 AM

The Effects of BACE and Its Targets on Age-related Seizures in Drosophila

Jereld R. Nicholson Library

The presence of Beta-Amyloid (Aβ) containing plaques in the brain is one of the histological hallmarks of Alzheimer’s Disease. β-secretase (BACE) is the enzyme responsible for producing this Aβ cleavage product and has also been shown to affect myelination and general neuronal activity. Observations from geriatric medicine suggest that there may be an increase in seizure activity associated with Alzheimer’s Disease. Preliminary data suggests that both over- and under-expression of BACE contributes to mechanically stimulated seizures in Drosophila. In vertebrates, seizure activity has been correlated with many factors including Neuregulin production and Na+ Pump activity. Both of these proteins have also been shown to require BACE activity for proper function. However, their roles in BACE related seizures remains unknown. Here we are following up on this preliminary study and exploring the roles of Vein (the Drosophila homolog of Neuregulin) and Numb (a negative regulator of the Notch Pathway). We have confirmed that any perturbation in dBACE (Drosophila BACE) levels causes a significant increase in age related seizures, suggesting that that BACE levels must be tightly regulated. In addition an increase of Vein levels also cause a dramatic increase in seizure amounts and duration suggesting that BACE, at least in part, is acting through this signaling pathway. Understanding which BACE related signaling pathways are responsible for age related seizure activity can lead to new treatments which will hopefully slow the progression of Alzheimer’s and other related neurodegenerative diseases.

 

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