Abstract: Currently, our understanding of the pathogenesis of major neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, is largely shaped by the amyloid cascade hypothesis. Particularly, this hypothesis posits that in Alzheimer’s disease, the aggregation of amyloid-beta peptide initiates a series of pathological processes leading to neuronal dysfunction and death (Zhang et al., 2024). Additionally, other mechanistic hypotheses, including tau protein hyperphosphorylation, metal ion dysregulation, and chronic neuroinflammation, contribute to the multifactorial nature of neurodegeneration. Such factors further exacerbate the impact of amyloids accumulation. These protein aggregates represent extremely stable structures that disrupt cellular functioning and initiate cascade inflammatory and oxidative processes, accelerating neurodegeneration. These processes involve microglial activation, inflammatory cytokine release, and impaired synaptic transmission, all exacerbating neuronal damage. Current treatments for neurodegenerative diseases linked to the accumulation of insoluble protein plaques focus mainly on symptomatic relief and slowing disease progression. For example, Alzheimer’s disease treatments often involve cholinesterase inhibitors and NMDA receptor antagonists (Cummings et al., 2023; Zhang et al., 2024). However, these drugs do not address one of the primary causes of degenerative changes—the accumulation of amyloid plaques (Zhang et al., 2023). Efforts to develop drugs targeting the degradation of amyloid fibrils and their aggregates have yet to yield effective and safe treatments. Several new medications following this approach, currently in various stages of development and clinical trials, have demonstrated limited efficacy despite initial optimism. In some cases, these drugs have caused serious side effects, such as brain edema and microhemorrhages (Zhang et al., 2023, 2024; Lasheen et al., 2024; Torres et al., 2024). Thus, despite years of research, no effective treatment has yet been developed to achieve the complete and safe degradation of amyloid fibrils. Challenges in developing an effective therapy for amyloidoses may partly arise from an insufficient understanding of the molecular mechanisms underlying the disruption of pathological aggregates by proposed drugs and the properties of amyloid degradation products. Obtaining such information is crucial for predicting the potential adverse effects of this therapy. In this regard, we aim to analyze the currently known mechanisms of amyloid degradation and evaluate their potential synergistic effects.