BACE 1 & Alzheimer’s Disease By Anisha Vora & Lindsey Wood What is Alzheimer’s? Neurodegenerative disorder characterized by the progressive and irreversible loss of nerve cells (neurons) located in the specific brain areas: the hippocampus and polymodal association areas
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By Anisha Vora & Lindsey Wood
Communication (sending messages)
Metabolism (turning chemicals and nutrients into energy to keep neurons working)
Repair (keeping long-lived neurons in good working order)
Cause nerve cells to stop working, lose connections w/ other cells and eventually die
Destruction causes memory failure, personality changes, etc.
Find abundance of β-amyloid plaques and neurofibrillary tangles, especially in regions for memoryPlaques & Tangles
APP is associated with the cell membrane, the thin barrier that encloses the cell. After it is made, APP sticks through the neuron's membrane, partly inside and partly outside the cell.
Enzymes act on the APP and cut it into fragments of protein, one of which is called beta-amyloid.
The beta amyloid fragments begin coming together into clumps outside the cell, then join other molecules and non-nerve cells to form insoluable plaques.
(Cai et al, 2001; Luo et al, 2001).
(Hong et al, 2000),
In vitro values
Cp P3 P1′ X BACE FRET HEK293 Aβ inhibition
at P3’ IC50(uM)a IC50(uM)a
1 CHMe2 Me N 0.082 (±0.023) 2.831 (±0.129)
2 — H H 9.704 (±1.413) >100
3 — Me H 0.285 (±0.016) >100
4 — Me N 4.925 (±0.169) >100
5 — Me H 2.397 (±0.089) >100
6 CHMe2 Me N 0.260(±0.002) 5.305 (±0.191)
7 (S)-MeCHEt(Ile) MeN 0.065 (±0.039) 0.880 (±0.042)
a Values are means of three experiments, standard deviation is given in parentheses.