-Synuclein Toxicity Biology of -Synuclein Maroteaux, et al. J. - - PowerPoint PPT Presentation

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Sep 02, 2023 485 likes •624 views

Determinants of -Synuclein Toxicity Biology of -Synuclein Maroteaux, et al. J. Neurosci. 1988 , 8 , 2804 Lashuel, et al. Nat. Rev. Neurosci. 2013 , 14 , 38 Pathology of -Synuclein Jucker, Walker. Nature 2013 , 501 , 45 -Synuclein

SLIDE 1

Determinants of α-Synuclein Toxicity

SLIDE 2

Biology of α-Synuclein

Lashuel, et al. Nat. Rev. Neurosci. 2013, 14, 38 Maroteaux, et al. J. Neurosci. 1988, 8, 2804

SLIDE 3

Pathology of α-Synuclein

Jucker, Walker. Nature 2013, 501, 45

SLIDE 4

α-Synuclein (Mis)Folding

SLIDE 5

Fowler, Fields. Nat. Methods 2014, 11, 801

Deep Mutational Scanning

SLIDE 6

The Model: Yeast

Khurana, Lindquist. Nat. Rev. Neurosci. 2010, 11, 436

SLIDE 7

Deep Mutational Scanning

SLIDE 8

Ries, Nussbaum-Krammer. Essays Biochem. 2016, 60, 181

α-Synuclein (Mis)Folding

SLIDE 9

Open Questions

What cellular stresses would make a cell more

susceptible to α-synuclein toxicity?

Is the toxicity of α-synuclein dependent on its

ability to engage different cellular factors?

What features or properties of α-synuclein enable

those cellular interactions?

Is the cell targeting particular structures or

residues of α-synuclein to mitigate toxicity?

SLIDE 10

A Chemical Biology Approach

SLIDE 11

Intellectual Contribution

– Conceive/revise/develop approaches – Analyze/interpret data

Technical Execution

– Do something to help the study be accomplished

Dissemination

– Describe your work and its implications – Certify the manuscript

Authorship Criteria

SLIDE 12

Goals for Today

Meet your groups
Come up with a name
Choose the compound for your experiment, give 1

minute presentation justifying the compound selection

Set up cluster access

SLIDE 13

Compound Choices

MG132
Brefeldin A
Tunicamycin
Geldanamycin
Miconazole
Menadione
Spermidine
TPCK
Dopamine
L-Dopa