This work focused on adding modularity and dynamic capability to this classical model by leveraging a multivalent macromolecular approach to TPD, where peptide amphiphiles were designed to self-assemble into high-aspect-ratio supramolecular nanofibers and present peptide epitopes on the surface of the fibers to target simultaneous binding of α-Syn.
This review summarizes recent advances in chemical protein degradation strategies for neurodegenerative disorders and highlights potential future perspectives of multifunctional PROTACs for therapeutic development.
Pasquale Degennaro, Imane Ghafir El Idrissi, Rosa Purgatorio et al.· Pharmaceuticals· 0 citations
Protein-Protein interactions are imperative for the regulation of a myriad of physiological processes including cellular homeostasis, cell signaling, immune response, genetic replication, and metabolism. Upon mutation or under conditions of cellular stress, proteins can become misfolded leading to aberrant Protein-Prot...
The ability of the 2D-FAST to discover potent antagonists of pathological proteins related to a wide range of diseases, including Alzheimer’s disease, is demonstrated.
It is proposed that a systems-level approach can be taken where PD is understood as a disease characterized by the imbalance in proteostasis, and potential treatment modalities include small molecules targeting lysosome function, CMA enhancers, gene therapy, and antibodies against extracellular α-synuclein.
Maryam Jabeen, Huma Hameed, Syed Muhammad Ahmad et al.· Neuromolecular medicine· 0 citations
Overall, the accumulated evidence indicates that phytochemicals possess multitarget therapeutic potential by simultaneously reducing protein aggregation, oxidative stress, mitochondrial dysfunction, and neuroinflammation, thereby offering broader neuroprotection than single-target approaches.
The Affinity-directed PROtein Missile system is employed and targeted degradation of α-synuclein impedes the pre-formed fibril (PFF)-induced aggregation of α-synuclein in primary neurons derived from rats expressing human α-synuclein.
Bill Carton, Géraldine Gelders, Gajanan Sathe et al.· npj Parkinson's Disease· 0 citations
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