Neural cell adhesion molecules in brain plasticity and disease

Gnanapavan, Sharmilee; Giovannoni, Gavin

doi:10.1016/j.msard.2012.08.002

Cited by 36 publications

(32 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results confirm lower levels of CSF sNCAM in MS patients compared to HC and in PMS compared to RRMS, [10][11][12][13] suggesting a reduced potential for regeneration and plasticity.…”

Section: Discussionsupporting

confidence: 84%

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS. Methods: We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured. Results: At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole.Conclusions: Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels. K E Y W O R D S Cerebrospinal fluid (CSF), Disease-modifying therapies (DMTs), EDSS, Multiple sclerosis (MS), Soluble neural cell adhesion molecule (sNCAM) | 423 AXELSSON Et AL. How to cite this article: Axelsson M, Dubuisson N, Novakova L, et al. Cerebrospinal fluid NCAM levels are modulated by disease-modifying therapies. Acta Neurol Scand.

show abstract

“…Our results confirm lower levels of CSF sNCAM in MS patients compared to HC and in PMS compared to RRMS, [10][11][12][13] suggesting a reduced potential for regeneration and plasticity.…”

Section: Discussionsupporting

confidence: 84%

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our study suggests that the aberrations of Np expression in these hippocampal areas are because of a response to attenuate the neuropathological changes caused by AD. This finding supports previously reported literature entailing alterations of CAMs in response to lesions that trigger a neurodegenerative pathological cascade …”

Section: Discussionsupporting

confidence: 93%

“…Data from mice and rats have allowed us to determine that neuroplastin has a high preference for the hippocampus and cerebellum, but only two studies have systematically analysed Np expression in human brains . As with other CAMs, it is presumed that Np is involved in the molecular events which underlay the structural and functional processes of brain development, ageing, and neurodegeneration . The adult human hippocampus retains a neuroplastic potential which enables it to remodel and reorganize after injury .…”

Section: Introductionmentioning

confidence: 99%

Hippocampal expression of cell‐adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Ilić

Mlinac-Jerkovic

Jovanov-Milošević

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Cell‐adhesion glycoprotein neuroplastin (Np) is involved in the regulation of synaptic plasticity and balancing hippocampal excitatory/inhibitory inputs which aids in the process of associative memory formation and learning. Our recent findings show that neuroplastin expression in the adult human hippocampus is specifically associated with major hippocampal excitatory pathways and is related to neuronal calcium regulation. Here, we investigated the hippocampal expression of brain‐specific neuroplastin isoform (Np65), its relationship with amyloid and tau pathology in Alzheimer's disease (AD), and potential involvement of neuroplastin in tissue response during the disease progression. Np65 expression and localization was analysed in six human hippocampi with confirmed AD neuropathology, and six age‐/gender‐matched control hippocampi by imunohistochemistry. In AD cases with shorter disease duration, the Np65 immunoreactivity was significantly increased in the dentate gyrus (DG), Cornu Ammonis 2/3 (CA2/3), and subiculum, with the highest level of Np expression being located on the dendrites of granule cells and subicular pyramidal neurons. Changes in the expression of neuroplastin in AD hippocampal areas seem to be related to the progression of disease. Our study suggests that cell‐adhesion protein neuroplastin is involved in tissue reorganization and is a potential molecular marker of plasticity response in the early neurodegeneration process of AD.

show abstract

“…These findings open up a new avenue for the exploration of the roles of PREP in processes involved in NCAM degradation, which, in turn, is believed to be one major contributor for altered neuroplasticity (Brusés and Rutishauser, 2001;Cremer et al, 1998;Gnanapavan and Giovannoni, 2013). Moreover, these mechanisms are of importance regarding synaptic plasticity in the (re-) organization of neuronal circuits.…”

Section: Discussionmentioning

confidence: 95%

Prolyl endopeptidase is involved in the degradation of neural cell adhesion molecules in vitro

Jaako

Waniek

Parik

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Membrane-associated glycoprotein neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) play an important role in brain plasticity by regulating cell-cell interactions. Here, we demonstrate that the cytosolic serine protease prolyl endopeptidase (PREP) is able to regulate NCAM and PSA-NCAM. Using a SH-SY5Y neuroblastoma cell line with stable overexpression of PREP, we found a remarkable loss of PSA-NCAM, reduced levels of NCAM180 and NCAM140 protein species, and a significant increase in the NCAM immunoreactive band migrating at an apparent molecular weight of 120 kDa in PREP-overexpressing cells. Moreover, increased levels of NCAM fragments were found in the concentrated medium derived from PREP-overexpressing cells. PREP overexpression selectively induced an activation of matrix metalloproteinase-9 (MMP-9), which could be involved in the observed degradation of NCAM, as MMP-9 neutralization reduced the levels of NCAM fragments in cell culture medium. We propose that increased PREP levels promote epidermal growth factor receptor (EGFR) signaling, which in turn activates MMP-9. In conclusion, our findings provide evidence for newlydiscovered roles for PREP in mechanisms regulating cellular plasticity through NCAM and PSA-NCAM.

show abstract

Neural cell adhesion molecules in brain plasticity and disease

Cited by 36 publications

References 75 publications

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

Hippocampal expression of cell‐adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Prolyl endopeptidase is involved in the degradation of neural cell adhesion molecules in vitro

Contact Info

Product

Resources

About