Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer’s disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD. In the nervous system, the interaction of metals with proteins appears to be an essential variable in the development or suppression of neurodegeneration. Chelation treatment may be an option for treating neurodegeneration induced by transition metal ion dyshomeostasis. Some clinicians even recommend using chelating agents as an adjunct therapy for AD. The current review also looks at the therapeutic strategies that have been attempted, primarily with metal-chelating drugs. Metal buildup in the nervous system, as reported in the AD, could be the result of compensatory mechanisms designed to improve metal availability for physiological functions.

Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with the pharmacological potency of small-molecule drugs. As an evolution beyond antibody–drug conjugates (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides a comprehensive analysis of the fundamental components of PDCs, including homing peptide selection, linker engineering, and payload optimization, alongside strategies to address their inherent challenges, such as stability, bioactivity, and clinical translation barriers. Therapeutic applications of PDCs span oncology, infectious diseases, metabolic disorders, and emerging areas like COVID-19, with several conjugates advancing in clinical trials and achieving regulatory milestones. Innovations, including bicyclic peptides, supramolecular architectures, and novel linker technologies, are explored as promising avenues to enhance PDC design. Additionally, this review examines the clinical trajectory of PDCs, emphasizing their therapeutic potential and highlighting ongoing trials that exemplify their efficacy. By addressing limitations and leveraging emerging advancements, PDCs hold immense promise as targeted therapeutics capable of addressing complex disease states and driving progress in precision medicine.

Proteins are vital for the regulation of several cellular functions, including the synthesis of structural components. The change in environmental conditions will impact conformational stability and result in aggregation. Protein aggregation involves different states of proteins, like nonnative, unfolded, and native states, which make them complex processes. The proper understanding of protein aggregation pathways involving the role of thermodynamically unfavoured lag phase, soluble protofibrils triggered polymerization through an exponential phase, and depleted free monomers owing to the saturation phase resulted in the leveling off of the polymerization process. The aggregated therapeutic proteins can induce deleterious immune responses in patients, and control of the aggregation is essential for better therapeutic protein stability and targeting with the help of stable protein structures and function. Protein–protein interactions (PPIs) are important for protein stability, aggregation rate, and solubility, while advanced computational and biophysical methods have been developed to characterize therapeutic protein aggregation better. Hence, an effective strategy for controlling, monitoring, and reproducing protein aggregation propensities of the polypeptide chains is required. An in-depth understanding of protein aggregation mechanisms, characterization, and combat strategies will counter the issues of protein aggregation. It will also reduce the cost of the product, time constraints, stable & effective product availability, and potential immunogenicity. Graphical Abstract