Current Understanding on the Role of Standard and Immunoproteasomes in Inflammatory/Immunological Pathways of Multiple Sclerosis

Table 1

Proteasome isoforms as potential targets of immunological pathways. The table summarizes the major results that may help future studies to understand how the inhibition of distinct proteasome isoforms may affect the development and progression of MS.

Final targets^a	Anatomic area	Proteasome subunits inhibited^b	MS forms	Potential effects^c	References
CD8^+ T cells	Thymus, lymph nodes, CNS	𝛽1i, 𝛽2i, 𝛽5i	NA	+/−	[22, 29, 38, 123, 124]
CD4^+ Th17 cells	Thymus, lymph nodes, CNS, gut	𝛽1i, 𝛽2i, 𝛽5i	NA	+	[51, 67, 68, 70, 72, 73]
B cells	Thymus, lymph nodes, CNS	𝛽1i	RR, PP, SP	+	[80, 81, 85]
Proteasome Abs	Serum	NA	RR, PP, SP	NA	[90]
Circulating proteasome	Serum	NA	NA	NA	[94, 99]
CNS parenchyma	CNS	𝛽5i	NA	−	[31]

aPathways that are directly or indirectly affected by treatment with proteasome inhibitors; ^bevidence from studies where the inhibition/depletion of specific proteasome subunit provided hints about their potential effect on MS; ^cthese effects also include speculative arguments on how the proteasome subunit inhibition may affect specific pathways. The detrimental or beneficial effects are marked as “−” or “+,” respectively; NA = not available evidence.