P11

The limitations on the use of fluoride therapy in dental caries prevention has necessitated the development of newer preventive agents. This review focusses on the recent and significant studies on P11-4 peptide with an emphasis on different applications in dental hard tissue conditions. The self-assembling peptide P11-4 diffuses into the subsurface lesion assembles into aggregates throughout the lesion, supporting the nucleation of de novo hydroxyapatite nanocrystals, resulting in increased mineral density. P11-4 treated teeth shows more remarkable changes in the lesion area between the first and second weeks. The biomimetic remineralisation facilitated in conjunction with fluoride application is an effective and non-invasive treatment for early carious lesions. Despite, some studies have reported that the P11-4 group had the least amount of remineralised enamel microhardness and a significantly lower mean calcium/phosphate weight percentage ratio than the others. In addition, when compared to a low-viscosity resin, self-assembling peptides could neither inhibit nor mask the lesions significantly. Moreover, when it is combined with other agents, better results can be achieved, allowing more effective biomimetic remineralisation. Other applications discussed include treatment of dental erosion, tooth whitening and dentinal caries. However, the evidence on its true clinical potential in varied dental diseases still remains under-explored, which calls for future cohort studies on its in vivo efficacy.

p11 (S100A10, annexin II light chain, calpactin I light chain) is a multifunctional protein that forms a heterotetrameric complex with Annexin A2, particularly at cell membranes. p11, alone or together with Annexin A2, interacts with several ion channels and receptors and regulates their cellular localization and function. Altered levels of p11 are implicated in the pathophysiology of several forms of cancer, psychiatric disorders, and neurodegeneration. Via interactions with ion channels and receptors, p11 modulates therapeutic actions of drugs targeting brain disorders. By serving as a plasminogen receptor, p11 plays an important role in plasmin generation, fibrinolysis, angiogenesis, tumor progression, and metastasis. Here, we review mechanisms whereby p11 regulates functions of ion channels and receptors in health and disease states.

The delayed behavioral response to chronic antidepressants depends on dynamic changes in the hippocampus. It was suggested that the antidepressant protein p11 and the chromatin remodeling factor SMARCA3 mediate this delayed response by inducing transcriptional changes in hippocampal neurons. However, what target genes are regulated by the p11/SMARCA3 complex to mediate the behavioral response to antidepressants, and what cell type mediates these molecular changes remain unknown. Here we report that the p11/SMARCA3 complex represses Neurensin-2 transcription in hippocampal parvalbumin-expressing interneurons after chronic treatment with Selective Serotonin Reuptake Inhibitors (SSRI). The behavioral response to antidepressants requires upregulation of p11, accumulation of SMARCA3 in the cell nucleus, and a consequent repression of Neurensin-2 transcription in these interneurons. We elucidate a functional role for p11/SMARCA3/Neurensin-2 pathway in regulating AMPA-receptor signaling in parvalbumin-expressing interneurons, a function that is enhanced by chronic treatment with SSRIs. These results link SSRIs to dynamic glutamatergic changes and implicate p11/SMARCA3/Neurensin-2 pathway in the development of more specific and efficient therapeutic strategies for neuropsychiatric disorders.