Deimination, Intermediate Filaments and Associated Proteins

Briot, Julie; Simon, Michel; Méchin, Marie-Claire

doi:10.3390/ijms21228746

Cited by 21 publications

(26 citation statements)

References 129 publications

(290 reference statements)

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“…How these changes contribute to neurodegeneration is not yet known. However, PC alters protein functions [9,14,50]. Furthermore, polypeptides relevant to neurodegeneration, such as amyloid β peptide, GFAP, vimentin, FET proteins, myelin proteins, and others, have been shown to be citrullinated [9,14,51,52].…”

Section: Discussionmentioning

confidence: 99%

Protein citrullination marks myelin protein aggregation and disease progression in mouse ALS models

Yusuf

Qiao

Parsi

et al. 2022

acta neuropathol commun

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Increased protein citrullination (PC) and dysregulated protein arginine deiminase (PAD) activity have been observed in several neurodegenerative diseases. PC is a posttranslational modification catalyzed by the PADs. PC converts peptidyl-arginine to peptidyl-citrulline, thereby reducing the positive charges and altering structure and function of proteins. Of the five PADs, PAD2 is the dominant isoform in the central nervous system (CNS). Abnormal PC and PAD dysregulation are associated with numerous pathological conditions, including inflammatory diseases and neurodegeneration. Animal model studies have shown therapeutic efficacy from inhibition of PADs, thus suggesting a role of PC in pathogenesis. To determine whether PC contribute to amyotrophic lateral sclerosis (ALS), a deadly neurodegenerative disease characterized by loss of motor neurons, paralysis, and eventual death, we investigated alterations of PC and PAD2 in two different transgenic mouse models of ALS expressing human mutant SOD1G93A and PFN1C71G, respectively. PC and PAD2 expression are altered dynamically in the spinal cord during disease progression in both models. PC and PAD2 increase progressively in astrocytes with the development of reactive astrogliosis, while decreasing in neurons. Importantly, in the spinal cord white matter, PC accumulates in protein aggregates that contain the myelin proteins PLP and MBP. PC also accumulates progressively in insoluble protein fractions during disease progression. Finally, increased PC and PAD2 expression spatially correlate with areas of the CNS with the most severe motor neuron degeneration. These results suggest that altered PC is an integral part of the neurodegenerative process and potential biomarkers for disease progression in ALS. Moreover, increased PC may contribute to disease-associated processes such as myelin protein aggregation, myelin degeneration, and astrogliosis.

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Section: Discussionmentioning

confidence: 99%

Protein citrullination marks myelin protein aggregation and disease progression in mouse ALS models

Yusuf

Qiao

Parsi

et al. 2022

acta neuropathol commun

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“…Although IFs are expressed in most cells, their expression is dynamic and subject to fine regulation involving post-translational modifications and intracellular proteolysis. In this Special Issue, the effects of deimination, a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs) were reviewed [1]. Deimination is related to physiological processes such as cell differentiation, embryogenesis, and innate and adaptive immunity, among others, and this modification has been associated with autoimmune diseases (rheumatoid arthritis, multiple sclerosis and lupus), cancers and neurodegenerative diseases.…”

mentioning

confidence: 99%

Recent Advances in Intermediate Filaments—Volume 1

Saéz

González-Granado

2022

IJMS

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“…FLG derives from a large precursor, pro-FLG contained into the KHGs of the stratum granulosum keratinocytes [ 22 ]. As keratinocytes cornify, pro-FLG undergoes dephosphorylation and enzymatic processing to deiminated filaggrin molecules dispersed in the corneocyte interior and becomes partially crosslinked to cornified envelopes [ 23 , 24 ]. Ultimately, free amino acids resulting from the filaggrin breakdown form the major part of the so-called natural moisturizing factor (NMF) of SC, presenting an exceptional water-holding capacity and contributing to the low pH of SC [ 25 ].…”

Section: Physical Protectionmentioning

confidence: 99%