Ruben Vidal, Ph.D.

Professor of Pathology and Laboratory Medicine

Ph.D. Biological Sciences, National University at Rosario, Argentina (1992)

Neurodegenerative diseases caused by abnormal protein deposition in the brain.

Fibrillization and aggregation of proteins in the brain is a common theme in a diverse group of neurodegenerative disorders. Insight into the pathogenesis of any one of these disorders may have implications for understanding the mechanisms that underlie all these diseases as well as for the discovery of better strategies to treat them. 

Research in my laboratory is focused on the molecular mechanisms by which deposition of a protein with an abnormal conformation causes neurodegeneration. We study the pathogenesis of Alzheimer disease (AD), familial British and Danish dementia (FBD and FDD), prion diseases, hereditary ferritinopathy (HF) and other neurodegenerative disorders in which the main biochemical event leading to brain degeneration involves the abnormal deposition of proteins in the brain parenchyma or in cerebral vessel walls. These are disorders of protein conformation leading to aggregation in which a protein that is present in body fluids as a soluble precursor deposits, producing organ dysfunction and cell death. In most cases, such as in AD, the abnormal protein is deposited as amyloid fibrils. Amyloid fibrils are composed of self-assembled, low molecular weight mass peptides adopting beta-pleated sheet structure, the conformation responsible for their physicochemical properties and tinctoreal characteristics. 

The association between protein aggregation and neurodegenerative diseases is an emerging field of study. We are investigating the genetic basis and the pathogenic mechanisms by which misfolded proteins cause neurodegeneration. To accomplish our goals we employ a multidisciplinary approach in which we use a variety of modern methodologies including molecular cloning, protein biochemistry, recombinant protein expression, cell transfection and transgenic animal models. Transgenic models are particularly important since they allow therapeutic approaches to be tested. As our understanding of the pathological mechanisms involved in neurodegenerative diseases increases, the hope for effective, novel therapeutic approaches is raised. Our research efforts are funded by grants from the National Institutes of Health (NIA and NINDS), the American Federation for Aging Research and the Alzheimer's Association.

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List of most Recent/Relevant Publications:

R. Vidal, B. Frangione, A. Rostagno, S. Mead, T. Revesz, G. Plant, and J. Ghiso. A stop-codon mutation in the BRI gene associated with familial British dementia.(1999) Nature 399:776-781.

R. Vidal, T. Révész, A. Rostagno, E. Kim, J. L. Holton, T. Bek, M. Bojsen-Møller, H. Braendgaard, G. Plant, J. Ghiso and B. Frangione. A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. (2000) Proc. Natl. Acad. Sci. U. S. A. 97: 4920-4925.

R. Vidal, B. Ghetti, M. Takao, C. Brefel-Courbon, E. Uro-Coste, B.S. Glazier, V. Siani, M.D. Benson, P. Calvas, L. Miravalle, O. Rascol, and M.B. Delisle. Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the Ferritin Light Polypeptide gene. (2004) J. Neuropathol. Exp. Neurol. 63:363-80.

L. Miravalle, M. Calero, M. Takao, A. E. Roher, B. Ghetti, and R. Vidal. Amino-terminally truncated Aβ peptide species are the main component of cotton wool plaques. (2005) Biochemistry. 44:10810-10821

M. A. Baraibar, A. G. Barbeito, B. M. Muhoberac, R. Vidal. Iron-mediated aggregation and a localized structural change characterize ferritin from a mutant light chain polypeptide that causes neurodegeneration. J Biol Chem 283(46):31679-89 (Published article online: Aug 28, 2008).

R. Vidal, L. Miravalle, X. Gao, A. Barbeito, M. Baraibar, S. K. Hekmatyar, M. Widel, N. Bansal, M. B. Delisle, B. Ghetti. (2008) Expression of a mutant form of the ferritin light chain gene induces neurodegeneration and iron overload in transgenic mice. J Neurosci 28(1):60-7.

R. Vidal, A. G. Barbeito, L. Miravalle, B. Ghetti. Cerebral amyloid angiopathy and parenchymal amyloid deposition in transgenic mice expressing the Danish mutant form of human BRI2. (2009) Brain Pathol. 19:58–68 (Published article online: Apr 10, 2008).

M. A. Baraibar, B. M. Muhoberac, H. J. Garringer, T. D. Hurley, R. Vidal. Unraveling of the E helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration. (2010) J Biol Chem 285(3):1950-6 (Published article Online: Nov 18, 2009)

M. A. Baraibar, B. M. Muhoberac, H. J. Garringer, T. D. Hurley, and R. Vidal. Unraveling of the E helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration. (2010) J. Biol. Chem. 285(3):1950-6. (Published article online: Nov 18, 2009)

R. Vidal, N. Sammeta, H. J. Garringer, K. Sambamurti, L. Miravalle, B. T. Lamb, and B. Ghetti. The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type amyloid precursor protein YAC transgenic mice. (2012) FASEB J. 26(7):2899-2910.

H. J. Garringer, J. Murrell, N. Sammeta, A. Gnezda, B. Ghetti, and R. Vidal. Increased tau phosphorylation and tau truncation, and decreased synaptophysin levels in mutant BRI2/tau transgenic mice. (2013) PLoS One 8(2):e56426. (Published article online: Feb 13, 2013). 

M. Pappolla, K. Sambamurti, R. Vidal, J. Pacheco, B. Poeggeler, and E. Matsubara. Evidence for Lymphatic Ab Clearance in Alzheimer’s Transgenic Mice. (2014) Neurobiol Dis 71:215-219. (Published article online: Aug 4, 2014). 

W. Li, H. J. Garringer, C. B. Goodwin, B. Richine, A. Acton, N. VanDuyn, B. B. Muhoberac, J. Irimia-Dominguez, R. J. Chan, M. Peacock, R. Nass, B. Ghetti, and R. Vidal. Systemic and cerebral iron homeostasis in ferritin knock-out mice (2014) PLoS One (In Press).

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