Nature Communication

Nature Communication

Relevance of the research

The Research is relevant in that it shows the roles of central nervous system in the development of multiple. Cell-permeable peptide, dNP2 efficiently delivers protein into to human T cells, and various tissues. When it enters in human brain tissues and the resident cells via blood vessels after penetrating tight, organized blood–brain barrier. The dNP2-conjugated cytoplasm domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows the inhibitory effect on autoimmune encephalomyelitis in preventive and therapeutic models, and that resulted in the reduction of the demyelization and CNS-infiltrating T helper 1 and T helper 17 cells. We learn that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 is an effective agent used when treating CNS inflammatory diseases such as MS.The inhibition of effectors T-cell functions by dNP2-ctCTLA-4 could modulate the progression of disease symptoms or enhances recovery without significant in vivo toxicity.

Research question addressed

The researchers are addressing the role of dNP2 from human NLBP as potent novel CPP .They further identifies delivery by dNP2 in primary T cells. More over it shows peptides and proteins several intracellular delivery mechanisms.

Hypothesis

1. Peptides and proteins have different intracellular delivery mechanisms.
2. Multiple sclerosis is as a result of induction of inflammation in the central nervous system by a myelin-specific T cells that cross the protective environment of the blood–brain barrier (BBB) 1.

Discussion on data

These results show dNP2 from human NLBP as a potent novel CPP that delivers functional macromolecules, like proteins, into cells both in vitro and in vivo without significant toxicit. Efficient protein delivery by dNP2 in primary T cells.CPPs are being evaluated in various cancer cell lines in vitro; their penetrating efficiency is lower in primary cells, thus severely limits the clinical applications of CPPs in humans30.Intracellular delivery mechanisms of dNP2 it is evident that peptides and protein have different intracellular delivery mechanisms from the data collected by the researchers. The data shows that the intracellular delivery device of dNP2 is identical to that reported for other CPPs, and applies several endocytosis pathways depending on cargos, such as lipid raft-mediated endocytosis following heparin sulfate interaction.dNP2 transports cargo proteins into the CNS in vivo. The high protein-delivery efficiency of dNP2 in primary T cells are difficult to transfect, us the researchers then were forced to carry investigation on the membrane-penetrating efficiency of dNP2 in the brain in the experiment on  Protein delivery efficiency of dNP2 in the brain and spinal cord. The research data shows that dNP2-ctCTLA-4 could regulate activated T-cell response in vitro and in vivo, and it can be seen as an immune-modulator protein to control CNS inflammatory diseases such as multiple sclerosis. The research is related to their conclusion we find it apparent that a novel and potent CNS-permeable peptide, dNP2, delivers macromolecules, such as proteins, into the brain and spinal cord. New therapies based on the use of dNP2 to deliver ctCTLA-4 into CNS-infiltrating T cells could be effective in regulating multiple sclerosis.

Weakness of the study

The current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS the research does not show functional sequence of Dnp2-ctCLA-4 to increase its efficiency and stability. It is true that researchers did not conduct enough research to answer the hypothesis .From data provided by the researchers is not clearly giving enough information and some points need further clarification. The data presentation can be easily misinterpreted and give wrong information from the figures. One needs time to read and understand the data moreover he or she needs knowledge on biology.