Title

Quantitative Analysis of the Autophagy-Lysosomal Pathway in Alzheimer's type Neurodegeneration

Authors

Daniella Amri

Document Type

Article

Publication Date

2009

Abstract

The proteotoxic peptide amyloid beta 42 (Ab42) is believed to play a causative role in Alzheimer?s disease. However, the mechanisms leading to the characteristic senile plaques and mass cell death are still unknown. The autophagy pathway is an underemphasized feature of the disease. Recent research has shown that neurons expressing Ab42 display an upregulation in the autophagy pathway through an accumulation of autophagy vesicles, autophagosomes, and autolysosomes in the cell. These subcellular vesicles become surrounded by cytoplasmic erosion eventually leading to cell death. Thus, it is our hypothesis that a malfunction of the autophagy-lysosomal pathway plays a key role in Ab42 induced Alzheimer type neurodegeneration. In this study I measured the total protein and enzyme activity for two different lysosomal hydrolases: Acid phosphatase and CathepsinD/E. My results provide important quantitative biochemical evidence in support of previous morphological and cell biological observations. Protein levels increase specifically in the Ab42 membrane fraction of Ab42 expressing 20 day old (dae) female flies. In addition, the activity of both autolysosomal (lysosomal) enzymes significantly increases in cytoplasm, which may indicate a compromise of the autolysomal (lysosomal) membrane as a consequence of Ab42 expression in neurons.

Advisor

Dr. Paul Salvaterra, City of Hope

Department

biochem

Support

Howard Hughes Medical Institute Undergraduate Science Education Grant



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