Post-translational Modifications of Proteins with Disordered Structure in the Regulation of Regeneration and Neurodegeneration of Brain Cells

This review focuses on the role of intrinsically disordered proteins and their post-translational modifications in the regulation of neuronal regeneration and neurodegeneration processes. Intrinsically disordered proteins, with their high conformational flexibility and lack of stable tertiary structure, can participate in a variety of cellular processes through dynamic and specific interactions with various partners. They are involved in the regulation of transcription, apoptosis, cell cycle, and stress responses. Key examples of such proteins are the transcription factors p53, c-Myc, FOXO3a, and E2F1, which, depending on the set of post-translational modifications, can switch between the functions of protecting neurons and activating their death. Particular attention is paid to the mechanisms by which post-translational modifications, such as acetylation, phosphorylation, and ubiquitination, alter the localization, stability, and activity of intrinsically disordered proteins affecting the outcome of cell fate. The contribution of misfolded proteins with structurally disordered domains, such as Tau and α-synuclein, to the pathogenesis of neurodegenerative diseases is also discussed. The article highlights the challenges associated with therapeutic targeting of such proteins due to their structural plasticity and diversity of post-translational modifications. Promising approaches to modulating the overall activity and functional state of target proteins are discussed, including modulation of the activity of post-translational modification enzymes and proteostasis mechanisms. The review illustrates the critical need for a comprehensive study of post-translational modifications as mechanisms of the disordered protein regulation for the development of new strategies for the treatment of acute nerve cell damage and neurodegenerative diseases.