Axonal damage is cause of major clinical disability in a wide range of neurological disorders, including multiple sclerosis (MS). Although considerable progress has been made in the detection of the early signs of axonal damage, still very little is known about the potential causative factors and the related signaling events. Thus, therapeutic approaches aimed at preventing or repairing damaged axons are not yet available. Our laboratory has recently reported the involvement of cytoplasmic HDAC1 in the impairment of mitochondrial transport and the onset of axonal swellings. This experimental plan proposes to characterize this novel intracellular signaling mechanism and use in vitro and in vivo models to characterize the role of specific isoforms of histone deacetylases in axonal damage in demyelinating disorders.
Axonal damage is cause of major clinical disability in a wide range of neurological disorders, including multiple sclerosis. Although considerable progress has been made in the detection of axonal damage in demyelinating disorders still very little is known about the underlying signaling events and this is the major focus of this grant. The results of the proposed experimental plan are expected to enhance our current state of knowledge on axonal damage and lead to the identification of potential novel therapeutic targets for multiple sclerosis and other disorders characterized by axonopathy.
|Zhu, Yunjiao; Vidaurre, Oscar G; Adula, Kadidia P et al. (2017) Subcellular Distribution of HDAC1 in Neurotoxic Conditions Is Dependent on Serine Phosphorylation. J Neurosci 37:7547-7559|
|Haines, Jeffery D; Vidaurre, Oscar G; Zhang, Fan et al. (2015) Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors. Mult Scler 21:1655-69|
|Haines, Jeffery D; Herbin, Olivier; de la Hera, Belén et al. (2015) Nuclear export inhibitors avert progression in preclinical models of inflammatory demyelination. Nat Neurosci 18:511-20|
|Gacias, Mar; Casaccia, Patrizia (2014) EPIGENETIC MECHANISMS IN MULTIPLE SCLEROSIS. Rev Esp Escler Mult 6:25-35|
|Vidaurre, Oscar G; Haines, Jeffery D; Katz Sand, Ilana et al. (2014) Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics. Brain 137:2271-86|
|Gacias, Mar; Casaccia, Patrizia (2013) Promoting return of function in multiple sclerosis: An integrated approach. Mult Scler Relat Disord 2:|
|Huynh, Jimmy L; Casaccia, Patrizia (2013) Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol 12:195-206|
|Vidaurre, Oscar G; Liu, Jia; Haines, Jeffery et al. (2012) An integrated approach to design novel therapeutic interventions for demyelinating disorders. Eur J Neurosci 35:1879-86|