Specialized roles of neurofilament proteins in synapses: Relevance to neuropsychiatric disorders

Abstract

Neurofilaments are uniquely complex among classes of intermediate filaments in being composed of four subunits (NFL, NFM, NFH and alpha-internexin in the CNS) that differ in structure, regulation, and function. Although neurofilaments have been traditionally viewed as axonal structural components, recent evidence has revealed that distinctive assemblies of neurofilament subunits are integral components of synapses, especially at postsynaptic sites. Within the synaptic compartment, the individual subunits differentially modulate neurotransmission and behavior through interactions with specific neurotransmitter receptors. These newly uncovered functions suggest that alterations of neurofilament proteins not only underlie axonopathy in various neurological disorders but also may play vital roles in cognition and neuropsychiatric diseases. Here, we review evidence that synaptic neurofilament proteins are a sizable population in the CNS and we advance the concept that changes in the levels or post-translational modification of individual NF subunits contribute to synaptic and behavioral dysfunction in certain neuropsychiatric conditions.

Effects of repetitive Iodine Thyroid Blocking on the Development of the Foetal Brain and Thyroid in rats: a Systems Biology approach

“…In the thyroid, DE genes are associated with transcription: sp1, ets1, pitx1 ; DNA binding: sp1, ets1, hist3h2ba, pitx1 ; as membrane components: stambp, olr278, kcnj15, extl3, lat2, ghitm, slc24a2, bcl2, glra2, gabbr1 . Certain of these genes, identified in the above functional groups, are important in the brain development 38–41 . However, to show how the above listed genes are interconnected, a network construction based on (DE) genes will help in understanding cellular processes that may be deregulated during ITB.…”

Intermediate filaments in developing neurons: Beyond structure

“…The synapse is thus likely a whole new locale where NFs act in neurons. Since altered NF distribution and phosphorylation have been implicated in neuropsychiatric and neurodegenerative disease models, NFs at synapses might have clinical relevance (Yuan & Nixon, ). The role of NFs at synapses is well reviewed in Yuan and Nixon ().…”

“…Since altered NF distribution and phosphorylation have been implicated in neuropsychiatric and neurodegenerative disease models, NFs at synapses might have clinical relevance (Yuan & Nixon, ). The role of NFs at synapses is well reviewed in Yuan and Nixon (). Even after many years of intensive research, much remains to be learned about the roles of mature NF networks in neurons!…”

“…The role of NFs at synapses is well reviewed in Yuan and Nixon (2016). Even after many years of intensive research, much remains to be learned about the roles of mature NF networks in neurons!…”

“…These might be toxic and lead to the dominant phenotypes of these disease‐associated alleles. Abnormal accumulation of IF proteins has also been noted in multiple degenerative diseases (Alzheimer's, Parkinson's, Huntington's, spastic paraplegia, spinal muscular atrophy, giant axonal neuropathy), neuropsychiatric disorders (drug addiction, schizophrenia, bipolar disorder), and others (cancer, diabetic neuropathy, traumatic brain injury) (Didonna & Opal, ; Eriksson et al, ; Godsel, Hobbs, & Green, ; Mahammad et al, ; Omary, ; Omary, Coulombe, & Mclean, ; Perrot, Berges, Bocquet, & Eyer, ; Perrot & Eyer, ; Sharma, Alsharif, Fallatah, & Chung, ; Yuan & Nixon, ). These diseases and disorders can often occur even in the apparent absence of mutations in the neuronal IF genes (Barry et al, ).…”