Development of monoclonal antibodies to target the large surface protein of hepatitis B virus and their use in therapeutic and diagnostic applications.

Over 250 million people are living with chronic infection caused by the hepatitis B virus (HBV). HBV has three surface proteins, namely small (SHBs), medium (MHBs) and large (LHBs), and they play different roles in the virus life cycle. The approved hepatitis B vaccine only contains the SHBs protein and many studies have focused on characterising the functional domains in SHBs. Although the LHBs protein is less studied, recent studies have shown that it plays important roles in mediating viral entry, replication and assembly. Over the years, there have been major advancements in monoclonal antibody (mAb) discovery tools and multiple mAbs have been developed to specifically target the preS1 domain in LHBs. We summarise the HBV infection systems and antibody discovery strategies that have been utilised by various research groups to assess the potential use of anti-preS1 mAbs as therapeutic antibodies against HBV or in the development of new diagnostic assays.

Improper Proteostasis: Can It Serve as Biomarkers for Neurodegenerative Diseases?

Cells synthesize new proteins after multiple molecular decisions. Damage of existing proteins, accumulation of abnormal proteins, and basic requirement of new proteins trigger protein quality control (PQC)-based alternative strategies to cope against proteostasis imbalance. Accumulation of misfolded proteins is linked with various neurodegenerative disorders. However, how deregulated components of this quality control system and their lack of general mechanism-based long-term changes can serve as biomarkers for neurodegeneration remains largely unexplored. Here, our article summarizes the chief findings, which may facilitate the search of novel and relevant proteostasis mechanism-based biomarkers associated with neuronal disorders. Understanding the abnormalities of PQC coupled molecules as possible biomarkers can help to determine neuronal fate and their contribution to the aetiology of several nervous system disorders.

Autophagy based cellular physiological strategies target oncogenic progression.

Evidence accumulated from past findings indicates that defective proteostasis may contribute to risk factors for cancer generation. Irregular assembly of abnormal proteins catalyzes the disturbance of cellular proteostasis and induces the ability of abnormal cellular proliferation. The autophagy mechanism plays a key role in the regular clearance of abnormal/poor lipids, proteins, and various cellular organelles. The results of functional and effective autophagy deliver normal cellular homeostasis, which establishes supportive metabolism and avoids unexpected tumorigenesis events. Still, the precise molecular mechanism of autophagy in tumor suppression has not been clear. How autophagy triggers selective or nonselective bulk degradation to dissipate tumor promotion under stress conditions is not clear. Under proteotoxic insults to knockdown the drive of tumorigenesis, it is critical for us to figure out the detailed molecular functions of autophagy in human cancers. The current article summarizes autophagy-based theragnostic strategies targeting various phases of tumorigenesis and suggests the preventive roles of autophagy against tumor progression. A better understanding of various molecular partners of autophagic flux will improve and innovate therapeutic approaches based on autophagic-susceptible effects against cellular oncogenic transformation.

Proteasome Based Molecular Strategies Against Improper Cellular Proliferation.

Cells contain several proteins that routinely fulfill multiple requirements for normal physiological survival. Proteostasis dysfunction is linked with different complex human disorders, like cancer, neuron degeneration, and imperfect aging. The ubiquitin proteasome system (UPS) forms the primary proteostasis mechanism taking part in cytoprotection. Cancer cells are well known to possess enhanced cytoprotective properties, and different UPS elements are implicated to be dysregulated at several stages of tumor progression. Furthermore, many studies have found tumor cells to exhibit higher levels of various UPS components, possibly contributing to their robust endurance. In this article, we have presented different cellular protein quality control strategies, essential for maintaining healthy proteome. Here, we have also discussed key contributions and functions of UPS involved in molecular pathomechanisms for establishing cancer conditions. Along with this, the emerging different therapeutic strategies against defective proteome linked with improper cellular proliferation and cancer progression are also reviewed. UPS performs critical regulatory functions in modulating the cellular apoptotic pathways. The proteasomal system involvement as probable therapeutic targets influencing cancer cell apoptosis is also discussed. Our article summarizes the recent developments in proteasome-associated pathways regulating tumor cell proteome and survival. Additionally, how the engagement and cross functions of these physiological processes can induce apoptosis and may develop regulation over tumor progression. A better understanding of multifaceted protein quality control pathways may inform therapeutic interventions based on cellular proteostasis response determined against complex diseases.