TY - JOUR
T1 - Genetic Convergence Brings Clarity to the Enigmatic Red Line in ALS
AU - Cook, Casey
AU - Petrucelli, Leonard
N1 - Funding Information:
This work was supported by the National Institutes of Health / National Institute of Neurological Disorders and Stroke ( R35NS097273 to L.P., P01NS084974 to L.P., U54NS100693 to L.P. and C.C.); Mayo Clinic Foundation (to L.P.); the Amyotrophic Lateral Sclerosis Association (to L.P.); the Robert Packard Center for ALS Research at Johns Hopkins (to L.P.); and the Target ALS Foundation (to L.P.).
Funding Information:
This work was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (R35NS097273 to L.P., P01NS084974 to L.P., U54NS100693 to L.P. and C.C.); Mayo Clinic Foundation (to L.P.); the Amyotrophic Lateral Sclerosis Association (to L.P.); the Robert Packard Center for ALS Research at Johns Hopkins (to L.P.); and the Target ALS Foundation (to L.P.).
Publisher Copyright:
© 2019
PY - 2019/3/20
Y1 - 2019/3/20
N2 - Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder that orchestrates an attack on the motor nervous system that is unrelenting. Recent discoveries into the pathogenic consequences of repeat expansions in C9ORF72, which are the most common genetic cause of ALS, combined with the identification of new genetic mutations are providing novel insight into the underlying mechanism(s) that cause ALS. In particular, the myriad of functions linked to ALS-associated genes have collectively implicated four main pathways in disease pathogenesis, including RNA metabolism and translational biology; protein quality control; cytoskeletal integrity and trafficking; and mitochondrial function and transport. Through the identification of common disease mechanisms on which multiple ALS genes converge, key targets for potential therapeutic intervention are highlighted. As efforts to develop a cure for amyotrophic lateral sclerosis are hampered by the lack of clarity in disease pathogenesis, Cook and Petrucelli review genetic causes and convergence on common pathways, providing insight into the underlying mechanisms that cause disease.
AB - Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder that orchestrates an attack on the motor nervous system that is unrelenting. Recent discoveries into the pathogenic consequences of repeat expansions in C9ORF72, which are the most common genetic cause of ALS, combined with the identification of new genetic mutations are providing novel insight into the underlying mechanism(s) that cause ALS. In particular, the myriad of functions linked to ALS-associated genes have collectively implicated four main pathways in disease pathogenesis, including RNA metabolism and translational biology; protein quality control; cytoskeletal integrity and trafficking; and mitochondrial function and transport. Through the identification of common disease mechanisms on which multiple ALS genes converge, key targets for potential therapeutic intervention are highlighted. As efforts to develop a cure for amyotrophic lateral sclerosis are hampered by the lack of clarity in disease pathogenesis, Cook and Petrucelli review genetic causes and convergence on common pathways, providing insight into the underlying mechanisms that cause disease.
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U2 - 10.1016/j.neuron.2019.02.032
DO - 10.1016/j.neuron.2019.02.032
M3 - Review article
C2 - 30897357
AN - SCOPUS:85062448692
SN - 0896-6273
VL - 101
SP - 1057
EP - 1069
JO - Neuron
JF - Neuron
IS - 6
ER -