Exploration of Neuroprotective Therapy

Table 3. Therapeutic strategies in multiple sclerosis.

Therapy	Place of action	Molecular target	Penetration in the BBB	Primary therapeutic mechanism
Raltegravir	CNS and periphery	Integrase of HERV-W	Yes	Inhibition of HERV-W integration reduces the expression of neurotoxic proteins associated with microglial activation and neurodegeneration.
Temelimab	CNS	HERV-W envelope protein	Not significant	Neutralization of the HERV-W envelope protein reduces microglial activation, inflammation, and toxicity on OL.
Ocrelizumab	Periphery	CD20 of B lymphocytes	No	Elimination of CD20+ B cells, reducing antigen presentation and production of pro-inflammatory cytokines.
Tolebrutinib	CNS and periphery	BTK	Yes	Inhibition of BCR and TLR signaling in B cells and microglia modulates compartmentalized inflammation in the CNS and chronic microglial activity.
N-Acetylglucosamine	CNS and periphery	Hexosamine pathway	Yes	Increased branching of N-glycans, promotes immune signaling regulation, reduces TH1/TH17 responses, microglial modulation, and supports remyelination.
Liothyronine	CNS	Thyroid hormone nuclear receptors	Yes	Stimulation of OPC differentiation and promotion of remyelination.
Clemastine	CNS	Muscarinic receptors	Yes	Removal of barriers to oligodendroglial differentiation.
Low-dose IL-2	Periphery	CD25 regulatory T cells	No	Expansion of regulatory T lymphocytes, restoring immune tolerance.
Ibudilast	CNS and periphery	Phosphodiesterases	Yes	Modulation of the immune system with reduced microglial activation, chronic inflammation, and progression of brain atrophy.

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BBB: blood-brain barrier; BTK: Bruton’s tyrosine kinase; CNS: central nervous system; HERV-W: human endogenous retrovirus-W; OL: oligodendrocyte; OPC: OL precursor cell; IL: interleukin; TLR: Toll-like receptor.

Declarations

Author contributions

CM and AV: Conceptualization, Investigation, Formal analysis, Writing—original draft, Writing—review & editing. AV: Visualization, Supervision, Validation, Funding acquisition. Both authors read and approved the submitted version.

Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.

Funding

This work was supported by the Portuguese Foundation for Science and Technology (FCT) through funding to the Research Centre for Natural Resources, Environment and Society—CERNAS [UIDB/00681]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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