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Neuroscience Work-in-Progress Seminar

Neurodegeneration in multiple sclerosis: a role for ceramide C16?


Mario Amatruda
Casaccia Lab, Advanced Science Research Center


Multiple Sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. Major progress has been made to understand and modulate the inflammatory component of MS, but the concomitant mechanisms contributing to neurodegeneration, which causes irreversible disability, remain largely unknown. We have recently discovered that ceramide C16 (a sphingolipid) is enriched in the cerebrospinal fluid of patients with MS, and that it is sufficient to induce mitochondrial respiration impairment and degeneration of neurons in vitro (Vidaurre et al., 2014). Here, we further examined the neurotoxic effect of ceramide C16. We show that ceramide C16 can readily enter into cultured neurons and accumulates in mitochondria changing their membrane potential and morphology. Furthermore, we found that neurons exposed to pro-inflammatory cytokines and oxidative stress are characterized by increased expression of the ceramide C16 synthetic enzymes (CerS5 and CerS6), suggesting that the endogenous, de novo synthesis of ceramide C16 could play a role in neurodegeneration during inflammation. Importantly, we discovered that transgenic mice (tg: CamKIIaCre;CerS5fl/flCerS6fl/fl) in which the neuronal synthesis of ceramide C16 is genetically inhibited, are protected during experimental autoimmune encephalomyelitis (EAE, a model of MS) from neurological deficit and neurodegeneration compared with wild type controls.

These findings raise the possibility that ceramide C16 can contribute, at least in part, to the mitochondrial dysfunction and neurodegeneration occurring in MS and the modulation of its synthesis may represent a novel therapeutic target.

The ASRC Neuroscience Work-in-Progress Seminars consist of an hour-long presentation on research relevant to the fields of neurobiology and translational neuroscience. Talks will be given by senior Ph.D. students, postdoctoral and faculty researchers. Anyone interested is encouraged to attend and actively participate in discussions.

Work-in-Progress Seminars are presented in collaboration with The City College of New York.

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Event Information

May 7, 2019
1:00 pm - 2:30 pm
ASRC 1st Floor Seminar Room
85 St. Nicholas Terrace
New York, NY 10031 United States
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