Abstract：
:Intermediate filament aggregation within motor neurons is a hallmark of ALS pathogenesis. Changes to intermediate filament stoichiometry due to altered mRNA steady-state levels of NEFL, PRPH and INA is thought to drive protein aggregation, yet the exact cause of these changes is unknown. MicroRNAs (miRNAs)-master regulators of gene expression-are largely dysregulated within ALS motor neurons and are known to be major contributors to the disease. We show that miR-105 and miR-9 are down-regulated within the spinal cord of ALS patients and target NEFL, PRPH and INA 3'UTRs to regulate gene expression. Further, both miR-105 and miR-9 were observed to regulate the mRNA stability of these three intermediate filaments endogenously within a neuronal-derived cell line. Our data demonstrates that miR-105 and miR-9 can regulate the mRNA stability of these key intermediate filaments and thus potentially contribute to the pathogenesis of intermediate filament inclusions in ALS.
journal_name
Brain Resjournal_title
Brain researchauthors
Hawley ZCE,Campos-Melo D,Strong MJdoi
10.1016/j.brainres.2018.10.032subject
Has Abstractpub_date
2019-03-01 00:00:00pages
93-100eissn
0006-8993issn
1872-6240pii
S0006-8993(18)30544-4journal_volume
1706pub_type
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