Journal Club 19th Feb. 2013. 3 years ago-------- cis, binding trans, not-binding 1.

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Journal Club 19th Feb. 2013. 3 years ago-------- cis, binding trans, not-binding 1

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

Sample VFFA replacing 3

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

Hypothesis for their experiment 5

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

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

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

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

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

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

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