Farnesol induces protection against murine CNS inflammatory demyelination and modifies gut microbiome

Sell, Lacey B.; Ramelow, Christina C; Kohl, Hannah M.; Hoffman, Kristina; Bains, Jasleen Kaur; Doyle, William J.; Strawn, Kevin D.; Hevrin, Theresa; Kirby, Trevor O.; Gibson, K. Michael; Roullet, Jean-Baptiste; Ochoa‐Repáraz, Javier

doi:10.1016/j.clim.2021.108766

Cited by 14 publications

(12 citation statements)

References 54 publications

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“…In this study, we did not attempt to ascertain the mode of action of farnesol in the promotion of myelination. Previously, farnesol efficacy was reported in treating multiple sclerosis, an inflammatory demyelinating disease of the CNS [33]. In EAE, a wellestablished model of multiple sclerosis, farnesol treatment delayed the onset of EAE and decreased disease severity.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, farnesol showed protective effects against neurodegenerative disease models and mitigated reactive gliosis in acrylamide-induced neurodegeneration [31,32]. It also significantly delayed the onset and decreased the disease severity of an experimental autoimmune encephalomyelitis (EAE) model [33]. Thus, we evaluated the therapeutic efficacy of farnesol for treating the demyelinating type of CMT using a CMT1A mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A

Park

Kwak

Doo

et al. 2021

CIMB

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Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol’s effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A

Park

Kwak

Doo

et al. 2021

CIMB

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“…However, there is the need for a wide-scale analysis of the sample to be transplanted, since the possibility exists, as it has occurred, that this material could contain dangerous toxins proceeding from unidentified pernicious bacteria hosted in the donor. A detailed explanation of this procedure, as well as of its possible problems and future prospects, can be seen in the recent review carried out by Ser et al [ 298 ].…”

Section: On Treatment Metabolically and Biochemically-derived Preclin...mentioning

confidence: 99%

Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on Multiple Sclerosis

Harguindey¹,

Alfarouk

Orozco³

et al. 2022

IJMS

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The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics of the cancer acid–base conceptual frame. At all levels of study (molecular, biochemical, metabolic, and clinical), the intimate nature of both processes appears to consist of opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranging original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows us to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) is an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Furthermore, within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth. Finally, and for the first time, a new and integrated model of treatment for MS can now be advanced.

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“…However, Farnesol is also attracting interest for tackling other neurological conditions and has already been shown to offer striking reductions in the severity of an immune response (autoimmune encephalomyelitis) in an experimental model of multiple sclerosis [ 40 ], a finding which could well lead to its clinical development for this condition. It is worth pointing out that those authors tentatively ascribe completely different biological actions of Farnesol to the beneficial response they have reported, including calcium channel inhibition, reduction of oxidative stress, attenuation of the inflammasome response, and lessening of pro-inflammatory cytokine secretion, some of which has previously been supported by others [ 41–46 ].…”

Section: Pd-relevant Properties Of Farnesolmentioning

confidence: 99%

Waiting for PARIS—A Biological Target in Search of a Drug

Wyse

Stott

Mursaleen

et al. 2022

JPD

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A recent breakthrough paper published in Science Translational Medicine has provided compelling evidence that inhibition of Parkin Interacting Substrate (PARIS) may offer clinical researchers an important new therapeutic approach since it shows considerable promise as an important biological target potentially capable of pharmaceutical intervention to slow long term neurodegeneration in patients with Parkinson’s disease (PD). We present several PD-relevant perspectives on this paper that were not discussed in that otherwise entirely scientific narrative. We also outline the some of the work leading up to it, including the massive drug screen that proved necessary to discover a clinically suitable inhibitor of PARIS (Farnesol), as well as relevant PD research within the wider drug class, issues surrounding its future formulation, and next steps in translating this new knowledge into the clinic to evaluate possible long-term PD patient benefits.

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Farnesol induces protection against murine CNS inflammatory demyelination and modifies gut microbiome

Cited by 14 publications

References 54 publications

Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A

Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A

Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on Multiple Sclerosis

Waiting for PARIS—A Biological Target in Search of a Drug

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