Abstract

GONZALEZ VELEZ, Jennifer; LEON BONIFACIO, Mariel; GARCIA HERRERA, Iris Paola  and  APARICIO VERA, Luis Alberto. Proteasome: its pathogenic role in autoimmune and autoinflammatory diseases. Rev. parag. reumatol. [online]. 2025, vol.11, n.2, pp.67-74.  Epub Dec 16, 2025. ISSN 2413-4341.  https://doi.org/10.18004/rpr/2025.11.02.67.

The proteasome and its immunoproteasome variant play essential roles in intracellular protein degradation, cell cycle regulation, and antigen presentation. Dysregulation of these complexes has been linked to the pathogenesis of various autoimmune and autoinflammatory diseases. This systematic review analyzed the available evidence regarding the pathogenic role of the proteasome in conditions such as rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren’s syndrome, multiple sclerosis, autoimmune thyroiditis, inflammatory bowel disease, and PRAAS syndromes. The immunoproteasome is highlighted as a key regulator of T-cell differentiation and pro-inflammatory cytokine production, while genetic mutations in proteasome subunits have been associated with autoinflammatory syndromes. Finally, the therapeutic potential of proteasome inhibitors such as bortezomib and ONX 0914 is discussed, showing promising preclinical results but requiring further studies to establish their safety and clinical applicability.

Keywords : proteasome; immunoproteasome; autoimmune diseases; autoinflammatory diseases.

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