TY - JOUR
T1 - Sporadic and hereditary amyotrophic lateral sclerosis (ALS)
AU - Ajroud-Driss, Senda
AU - Siddique, Teepu
N1 - Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
AB - Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
KW - Familial ALS
KW - Paradigm shift
KW - Pathogenesis
KW - Sporadic ALS
UR - http://www.scopus.com/inward/record.url?scp=84922318925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922318925&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2014.08.010
DO - 10.1016/j.bbadis.2014.08.010
M3 - Review article
C2 - 25193032
AN - SCOPUS:84922318925
SN - 0925-4439
VL - 1852
SP - 679
EP - 684
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 4
ER -