1. Journal Club 19th Feb
3 years ago
cis, binding
trans, not-binding 1

2. Pathogenesis of Alzheimer’s disease
Introduction
Pathogenesis of Alzheimer’s disease
One of the candidate for hypothesis
42-residue amyloid b-peptide (Ab1-42)
Forming fibrillar aggregation
Toxic to cells
However, larger fibrils are non-toxic.
a-helix to b-pleated sheets conversion
M. Ahmed et al., 2010, Nat. Struct. Mol. Biol. 2

3. Sample
VFFA
replacing 3

4. Incubation in routine way
Method; MTT assay
SH-SY5Y cells
Incubation in routine way
Medium was replaced by medium containing samples.
Lysing cells
Monitoring MTT (indicating compounds) reduction.
Harmeier et al., 2009, J. Neurosci. 4

5. Hypothesis for their experiment5

6. Disassembled cis-Ab-photo-peptides are toxic.
Results & Discussion
MTT assay
Disassembled cis-Ab-photo-peptides are toxic. 6

7. SEC Freshly-dissolved native Ab1-42 toxic
cis-disassembled photo-Ab1-42
toxic 7

8. Freshly-dissolved trans photo-Ab1-42
toxic
The profiles are different among three samples, but all of them showed toxicity.
My opinion
The authors should show the profiles in case of trans photo-Ab1-42, which was non-toxic. 8

9. a-helix conformation is toxic.
CD Analysis
(20% HFIP/80% phosphate buffer, pH 7.4)
hexafluoroisopropanol
2 days after, trans
non-toxic
2 days after, cis
Fresh trans
toxic
Fresh cis
a-helix conformation is toxic. 9

10. TEM image
2 days after, trans
2 days after, cis
No assay data 10

11. non-toxic
trans-to-cis
may be toxic
may be toxic
Fresh trans
Fresh cis
Native
toxic
toxic
toxic 11

12. Conclusion
Controlling structural changes through light-induced isomerization of the embedded
switch unit.
The toxicity of the photo Ab is almost independent of the isomeric state of the
incorporated azo-unit and comparable to that of Ab, but the photoisomers differ
in the distribution of distinct oligomers.
The fact might provide answers to the questions of how the different
oligomers can cause cell death in follow-up studies.
The transition between monomers and fibrils proceeds mainly through two soluble
oligomer states-tetra- to hexamers and ~18-mers.
toxic
My opinion: They should show the SEC profile of trans-photo fibrils. 12