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Resistance versus vulnerability: unraveling the fate of neuronal subtypes in neuropathologies

CMCB Green Seminar

Datum:25.01.2019, 11:00 - 12:00
Sprecher: Dr. Natalia Rodriguez-Muela, Harvard University, Dept. Stem Cell and Regenerative Biology & Biological Research Center-Spanish National Research Council - Dept. Cellular and Molecular Biology
Ort: CRTD, auditorium left
Gastgeber: Dr. Jared Sterneckert


Why a given neuropathology does not impact all neurons of the same type to a similar level? This is a fascinating question in neurodegeneration research that remains unanswered.

In most neurodegenerative diseases certain neuronal subgroups degenerate fast while others, carrying the same mutations -if any-, subjected to theoretically analogous stress and displaying comparable functional properties remain unaffected, even at the latest stages of the disease. Motor neuron diseases are a group of disorders in which motor neurons (MNs) of the spinal cord and/or the motor cortex are the primary cell type affected where this perplexing feature can also be observed.

Using a variety of approaches ranging from cellular biology techniques and live imaging to genome editing and single cell genomics, and utilizing hiPSC together with transgenic animal models, we investigate the molecular mechanisms underlying such selective MN death. We devote a special focus at exploring the molecular basis of proteostasis failure -major causative event in neurodegeneration-, and at examining the contribution of cell autonomous and non-cell autonomous factors to the selective MN loss. Our ultimate goal is to understand the molecular cause of this distinctive neuronal vulnerability to design effective therapeutics targeting specific neuronal subtypes or phases of the disease.

5 most recent papers

1. Rodriguez-Muela N*, Parkhitko A, Grass T, Gibbs R, Norabuena E, Perrimon N, Singh R, Rubin LL*. Blocking p62/SQSTM1- dependent SMN degradation ameliorates the Spinal Muscular Atrophy disease phenotype. (*Corresponding authors; J Clin Invest. 2018 Jul 2;128(7):3008-3023; highlighted in "JCI This Month" for July2018 Issue, reference 95231).

2. Rodriguez-Muela N1*, Litterman NK1, Norabuena EM, Mull JL, Galazo MJ, Sun C, Ng SY, Makhortova NR, White A, Lynes MM, Chung WK, Davidow LS, Macklis JD, Rubin LL*. Single-Cell Analysis of SMN Reveals Its Broader Role in Neuromuscular Disease. Cell Reports. 2017 Feb 7;18(6):1484-1498 (*Corresponding authors, 1equal contribution).

3. Ng SY1, Soh BS1, Rodriguez-Muela N, Hendrickson DG, Price F, Rinn JL, Rubin LL. Genome-wide RNA-Seq of Human Motor Neurons Implicates Selective ER Stress Activation in Spinal Muscular Atrophy. Cell Stem Cell. 2015 Nov 5;17(5):569-84 (1equal contribution).

4. Rodríguez-Muela N, Koga H, et al.. Balance between autophagic pathways preserves retinal homeostasis. Aging Cell. 2013 Jun;12(3):478-88. (Featured on Aging Cell cover, June 2013 vol 12).

5. Rodríguez-Muela N, Germain F, et al.. Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice. Cell Death Differ. 2012 Jan;19(1):162-9. (Awarded "Article of the month" by SEBBM, July 2011)

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