Insights into mechanism of ionic liquids for protein stability: Future implications for neurodegeneration treatment

Neurodegenerative diseases are characterized by a gradual loss of neurons, cellular dysfunction, loss of intricate synaptic networks and brain damage, which are going to be the second leading cause of death in future. These proteinopathies are marked by abnormal amyloid fibril deposition, aberrant aggregation of misfolded proteins via polymerization, where protein aggregates serve as key pathological hallmarks in Alzheimer's, Parkinson's, and multiple system atrophy disorders. These toxic aggregates accumulate in the brain and disrupt neuronal function, targeting motor neurons, spinal cord, and ultimately leading to respiratory failure and death. As population ages, the prevalence of these neuronal disorders rises significantly, emphasizing to approach effective treatment for risk reduction. In the pursuit of developing effective anti-amyloidogenesis therapeutic agents, ionic liquids (ILs) continue to receive the least attention. ILs have emerged as promising substitute for conventional solvents, owing to their unique physicochemical properties that facilitate protein refolding, mitigate denaturation, amyloidogenesis, and prevent aggregation. This review critically addresses intricate IL-protein interactions, dictated by anions-cations composition of ILs, their polarity, hydrophobicity, kosmotropicity, chaotropicity, amphiphillicity, and network, which modulate protein behavior and support structural and functional integrity. This article also underscores the need for precision in IL selection, ensuring their properties align with the desired structural outcome. We showcase ILs as a promising therapeutic avenue for neurodegenerative diseases, demonstrating their potential to modulate pathological protein aggregation and enhance protein homeostasis. Lastly, this review of outstanding research works, account for current lacunae that will guide future perspectives for the rational designing of IL for protein stabilization and offers new strategies for addressing underlying mechanism of ageing disorders.