Post-transcriptional control of neurofilaments in development and disease.
Tight coordination of the expression of neurofilament subunits is integral to the normal development and function of the nervous system. Imbalances in their expression are increasingly implicated in the induction of neurodegeneration in which formation of neurofilamentous aggregates is central to the pathology. Neurofilament expression can be controlled not only at the transcriptional level but also through post-transcriptional regulation of mRNA localization, stability, and translational efficiency. The critical role that post-transcriptional mechanisms play in maintaining neurofilament homeostasis is highlighted, for example, by the human disease amyotrophic lateral sclerosis, in which selective destabilization of NF-L mRNA (or failure to stabilize it) is associated with the formation of neurofilamentous aggregates - a hallmark of the disease process. This review discusses the post-transcriptional regulatory mechanisms and associated ribonucleoproteins that have been implicated to date in controlling neurofilament expression during normal development and in disrupting neurofilament homeostasis during neurodegenerative disease.
Thyagarajan
Amar
A
Department of Biological Sciences and the Neuroscience Research Center, University at Albany, SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.
Strong
Michael J
MJ
Szaro
Ben G
BG
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; D016900:Neurofilament Proteins; D012333:RNA, Messenger