The role of scaffold is essential for the organization and regulation of cellular signalling pathways, acting proteins as molecular frameworks that unite various signalling molecules and facilitate their interaction and coordination¹. The significance of scaffold proteins in human diseases is vast, as they can influence the development, progression, and treatment of various conditions. Understanding importance of scaffold proteins in different cellular processes is vital for figuring out the pathophysiology of diseases that affect mankind, such as cancer progression, neurological disorders, immune system regulation, cardiovascular diseases, and metabolic disorders. Targeting scaffold proteins or their corresponding signaling channels might provide fresh approaches to treating a range of illnesses¹.

Protein Scaffolds in Cancer Diagnosis and Therapy

Protein scaffolds have shown promising potential as alternatives to antibodies for cancer diagnosis and therapy. They have been utilized extensively not only in cancer imaging and therapy but also in basic research, such as detection and elimination of microbes, intracellular delivery, blocking of the signal pathway, crystallization analysis, and in vitro detecting probes². The development of computer simulation, molecular docking, and experimental technologies has led to the emergence of safer, more effective, and affordable novel scaffolds.

The smaller molecular size of protein scaffolds (<20 kDa) facilitates tissue infiltration and deeper tumor lesion penetration, making them suitable for targeting proteins such as Ras and Myc, which are impossible to approach using conventional antibodies². The favorable physicochemical stability of scaffold binders is also appealing, as they can refold to their original structure after experiencing extreme temperature changes or following broad pH changes. Some of them, such as knottin scaffolds, are able to withstand even higher temperatures (over 100 °C), making efficient coupling and photothermal reaction possible².

Scaffold Proteins in Autoimmune Disorders

In autoimmune settings such as lupus, scaffold proteins can lower the cell activation threshold, resulting in uncontrolled signaling and hyperactivity⁴. Scaffold proteins, through their binding domains, mediate protein-protein interaction and play numerous roles in cellular communication and homeostasis. An overview is provided through this study on scaffold proteins, their influence on the different signalling pathways, and their role in the pathogenesis of autoimmune and auto inflammatory diseases. Since these proteins participate in many roles and interact with numerous more signaling pathways, it is necessary to gain a thorough understanding of these proteins and their nuances to facilitate effective target identification and therapeutic design for the treatment of autoimmune disorders⁴.

Protein-scaffolding for Repairing DNA Damage

Lack of scaffolding cause diseases such as cancer. When the scientists prevented cells to build the protein scaffold around fractured DNA, they observed that large sections of the neighbouring chromosome rapidly fell apart. This caused DNA-damaged cells to start alternative attempts to repair themselves, but this approach is often futile and exacerbated the destruction of the genetic material. As per the researchers, this explains why those who are deficient in scaffold proteins are more likely to get sick caused by unstable DNA³.

Conclusion

Understanding the role of scaffold proteins in human diseases is crucial for the development of new therapeutic strategies. Targeting scaffold proteins or their corresponding signalling pathways may offer new opportunities for the treatment of various disorders, including cancer, neurological disorders, immune system regulation, cardiovascular diseases, and metabolic disorders. The emerging role of scaffold proteins in the treatment of various diseases is a potential area that needs more investigation and study.