@article {1445346,
	title = {Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Jun 03},
	abstract = {In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial motor neurons (CrMN) are spared until late stages of the disease. Using a rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) to SpMNs and CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time. ESC-derived CrMNs have higher proteasome activity to degrade misfolded proteins and are intrinsically more resistant to chemically-induced proteostatic stress than SpMNs. Chemical and genetic activation of the proteasome rescues SpMN sensitivity to proteostatic stress. In agreement, the hSOD1 G93A mouse model reveals that ALS-resistant CrMNs accumulate less insoluble hSOD1 and p62-containing inclusions than SpMNs. Primary-derived ALS-resistant CrMNs are also more resistant than SpMNs to proteostatic stress. Thus, an ESC-based platform has identified a superior capacity to maintain a healthy proteome as a possible mechanism to resist ALS-induced neurodegeneration.},
	issn = {2050-084X},
	doi = {10.7554/eLife.44423},
	author = {An, Disi and Fujiki, Ryosuke and Iannitelli, Dylan E and Smerdon, John W and Maity, Shuvadeep and Rose, Matthew F and Gelber, Alon and Wanaselja, Elizabeth K and Yagudayeva, Ilona and Lee, Joun Y and Vogel, Christine and Wichterle, Hynek and Engle, Elizabeth C and Mazzoni, Esteban Orlando}
}
