Cryo-EM: Developing ALS Therapies in a Flash Freeze?

October 18, 2017 - als

Flash solidify frames. The disaggregase Hsp104 pulls out one protein from an aggregate, dual amino acids during a time, regulating a ratchet-like resource according to a new cryo-EM investigate led by Daniel Southworth in partnership with James Shorter.[Reprinted with accede from Gates et al., 2017, Science/AAAS]. .]

The inventors of cryo-electron microscopy snapped adult a Nobel Prize in Chemistry this month (see October 2017 news). The constructional technique, pioneered in a mid-1970s, is rising as a pivotal proceed to breeze molecular blueprints of formidable intracellular structures including a chief pore, that might burden adult in ALS (see August 2015 news; for review, see Hoelz et al., 2016).

The plan recently enabled Daniel Southworth’s group during a University of Michigan to constraint molecular snapshots of Hsp104, an enzyme that helps refold many-sided proteins (Gates et al., 2017).The proceed is now being grown by University of Pennsylvania School of Medicine’s James Shorter as a intensity therapy for ALS (see September 2017 news). Efforts to optimize this proceed regulating these molecular blueprints, are now underway.

***

To learn some-more about how scientists aim to precedence existent enzymes to bust adult inclusions in ALS, check out a new feature: Breaking up TDP-43 aggregates might be doable.

References

Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR. Ratchet-like polypeptide translocation resource of a AAA+ disaggregase Hsp104. Science. 2017 Jul 21;357(6348):273-279. [PubMed].

Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S, Lee KH, Badders N, Valentine M, Miller BL, Wong PC, Petrucelli L, Kim HJ, Gao FB, Taylor JP.GGGGCC repeat enlargement in C9orf72 compromises nucleocytoplasmic transport. Nature. 2015 Sep 3;525(7567):129-33. doi: 10.1038/nature14974. Epub 2015 Aug 26. [PubMed].

Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE, Rothstein JD. The C9orf72 repeat enlargement disrupts nucleocytoplasmic transport. Nature. 2015 Sep 3;525(7567):56-61. [PubMed].

Further Reading

Earl LA, Falconieri V, Milne JL, Subramaniam S. Cryo-EM: over a microscope. Curr Opin Struct Biol. 2017 Jun 21;46:71-78. [PubMed].

Kim HJ, Taylor JP. Lost in Transportation: Nucleocytoplasmic Transport Defects in ALS and Other Neurodegenerative Diseases. Neuron. 2017 Oct 11;96(2):285-297. [PubMed].

Shorter J. Designer protein disaggregases to opposite neurodegenerative disease. Curr Opin Genet Dev. 2017 Jun;44:1-8. [PubMed].

Share this:
Facebooktwittergoogle_plusmailFacebooktwittergoogle_plusmail

source ⦿ http://www.alsresearchforum.org/cryo-em-developing-als-therapies-in-a-flash-freeze/

More als ...

› tags: als /