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Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease.
Front Immunol. 2018; 9:2784.FI

Abstract

Though promoting remyelination in multiple sclerosis (MS) has emerged as a promising therapeutic strategy, it does not address inflammatory signals that continue to induce neuronal damage and inhibit effectiveness of repair mechanisms. Our lab has previously characterized the immunomodulatory tetrapeptide, tuftsin, which induces an anti-inflammatory shift in microglia and macrophages. This targeted anti-inflammatory agent improves physical deficits in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we sought to determine whether tuftsin is also effective in combination with benztropine, an FDA-approved drug that stimulates remyelination, in both EAE and in the cuprizone model of demyelination. We show that combining these two agents to promote anti-inflammatory and remyelinating mechanisms alleviates symptoms in EAE and lessens pathological hallmarks in both MS models. Importantly, tuftsin is required to transform the inflammatory CNS environment normally present in EAE/MS into one of an anti-inflammatory nature, and benztropine is required in the cuprizone model to improve remyelination. Our data further support tuftsin's beneficial immunomodulatory activity in the context of EAE, and show that when studying remyelination in the absence of an autoimmune insult, tuftsin still activated microglia toward an anti-inflammatory fate, but benztropine was necessary for significant repair of the damaged myelin. Overall, tuftsin effectively combined with benztropine to significantly improve MS-like pathologies in both models.

Authors+Show Affiliations

Program in Molecular and Cellular Pharmacology, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, United States.Program in Molecular and Cellular Pharmacology, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, United States. Department of Biological Sciences, State University of New York, College at Old Westbury, Old Westbury, NY, United States.Program in Molecular and Cellular Pharmacology, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, United States.Program in Molecular and Cellular Pharmacology, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30555470

Citation

Thompson, Kaitlyn K., et al. "Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease." Frontiers in Immunology, vol. 9, 2018, p. 2784.
Thompson KK, Nissen JC, Pretory A, et al. Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease. Front Immunol. 2018;9:2784.
Thompson, K. K., Nissen, J. C., Pretory, A., & Tsirka, S. E. (2018). Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease. Frontiers in Immunology, 9, 2784. https://doi.org/10.3389/fimmu.2018.02784
Thompson KK, et al. Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease. Front Immunol. 2018;9:2784. PubMed PMID: 30555470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tuftsin Combines With Remyelinating Therapy and Improves Outcomes in Models of CNS Demyelinating Disease. AU - Thompson,Kaitlyn K, AU - Nissen,Jillian C, AU - Pretory,Amanda, AU - Tsirka,Stella E, Y1 - 2018/11/28/ PY - 2018/05/23/received PY - 2018/11/12/accepted PY - 2018/12/18/entrez PY - 2018/12/18/pubmed PY - 2019/10/3/medline KW - anti-inflammatory KW - autoimmunity KW - combination KW - microglia KW - remyelination KW - therapy KW - tuftsin SP - 2784 EP - 2784 JF - Frontiers in immunology JO - Front Immunol VL - 9 N2 - Though promoting remyelination in multiple sclerosis (MS) has emerged as a promising therapeutic strategy, it does not address inflammatory signals that continue to induce neuronal damage and inhibit effectiveness of repair mechanisms. Our lab has previously characterized the immunomodulatory tetrapeptide, tuftsin, which induces an anti-inflammatory shift in microglia and macrophages. This targeted anti-inflammatory agent improves physical deficits in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we sought to determine whether tuftsin is also effective in combination with benztropine, an FDA-approved drug that stimulates remyelination, in both EAE and in the cuprizone model of demyelination. We show that combining these two agents to promote anti-inflammatory and remyelinating mechanisms alleviates symptoms in EAE and lessens pathological hallmarks in both MS models. Importantly, tuftsin is required to transform the inflammatory CNS environment normally present in EAE/MS into one of an anti-inflammatory nature, and benztropine is required in the cuprizone model to improve remyelination. Our data further support tuftsin's beneficial immunomodulatory activity in the context of EAE, and show that when studying remyelination in the absence of an autoimmune insult, tuftsin still activated microglia toward an anti-inflammatory fate, but benztropine was necessary for significant repair of the damaged myelin. Overall, tuftsin effectively combined with benztropine to significantly improve MS-like pathologies in both models. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/30555470/Tuftsin_Combines_With_Remyelinating_Therapy_and_Improves_Outcomes_in_Models_of_CNS_Demyelinating_Disease L2 - https://doi.org/10.3389/fimmu.2018.02784 DB - PRIME DP - Unbound Medicine ER -