TY - JOUR 
A1 - Todd, T. W.
AU - McEachin, Z. T.
AU - Chew, J.
AU - Burch, A. R.
AU - Jansen-West, K.
AU - Tong, J. M.
AU - Yue, M.
AU - Song, Y. P.
AU - Castanedes-Casey, M.
AU - Kurti, A.
AU - Dunmore, J. H.
AU - Fryer, J. D.
AU - Zhang, Y. J.
AU - San Millan Tejado, Beatriz
AU - Teijeira Bautista, Susana
AU - Arias Gómez, Manuel
AU - Dickson, D.
AU - Gendron, T. F.
AU - Sobrido Gómez, María Jesús
AU - Disney, M. D.
AU - Bassell, G. J.
AU - Rossoll, W.
AU - Petrucelli, L.
T1 - Hexanucleotide Repeat Expansions in c9FTD/ALS and SCA36 Confer Selective Patterns of Neurodegeneration In Vivo
Y1 - 2020
SN - 2211-1247
UR - http://hdl.handle.net/20.500.11940/16702
AB - A G4C2 hexanucleotide repeat expansion in an intron of C9orf72 is the most common cause of frontal temporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). A remarkably similar intronic TG3C2 repeat expansion is associated with spinocerebellar ataxia 36 (SCA36). Both expansions are widely expressed, form RNA foci, and can undergo repeat-associated non-ATG (RAN) translation to form similar dipeptide repeat proteins (DPRs). Yet, these diseases result in the degeneration of distinct subsets of neurons. We show that the expression of these repeat expansions in mice is sufficient to recapitulate the unique features of each disease, including this selective neuronal vulnerability. Furthermore, only the G4C2 repeat induces the formation of aberrant stress granules and pTDP-43 inclusions. Overall, our results demonstrate that the pathomechanisms responsible for each disease are intrinsic to the individual repeat sequence, highlighting the importance of sequence-specific RNA-mediated toxicity in each disorder.
KW - Humans
KW - RNA
KW - Neurons
KW - Amyotrophic Lateral Sclerosis
KW - Mice
KW - Inclusion Bodies
KW - DNA Repeat Expansion
KW - Animals
KW - Frontotemporal Dementia
KW - Nuclear Proteins
KW - ARN
KW - proteínas nucleares
KW - neuronas
KW - expansión de las repeticiones de ADN
KW - animales
KW - humanos
KW - esclerosis lateral amiotrófica
KW - cuerpos de inclusión
KW - demencia frontotemporal
KW - ratones
KW - Amyotrophic Lateral Sclerosis
KW - Animals
KW - DNA Repeat Expansion
KW - Frontotemporal Dementia
KW - Humans
KW - Inclusion Bodies
KW - Mice
KW - Neurons
KW - Nuclear Proteins
KW - RNA
KW - CHUS
KW - CHUVI
KW - IDIS
ER -