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Jorge A. Ghiso

Jorge A. Ghiso, PhD

Professor, Department of Pathology

Professor, Department of Psychiatry

Keywords
genetic and biochemical basis of Alzheimer Disease, molecular, cellular, & translational neuroscience
Summary

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive memory and cognitive decline during mid to late adult life. At least four genes have been implicated in the pathogenesis of this disease: 1) The APP gene located on chromosome 21, codifies for the precursor protein of amyloid b (Ab), the main component of the fibrils deposited in cerebral vessel walls and parenchymal senile plaques characteristic of AD. 2) The APOE gene located on chromosome 19, codifies for several apolipoprotein E isoforms. The e4 allele is associated with late-onset AD and its inheritance is considered a risk factor for AD. 3) The presenilin 1 (PS1) gene, located on chromosome 14, and 4) the presenilin 2 (PS2) gene mapped to chromosome 1 were found linked to early-onset familial AD. These two genes codify for two highly homologous transmembrane proteins with still unknown biological function(s). Products of these genes (APP, its degradation product Ab, apoE, and presenilins) are present in Alzheimer amyloid lesions. Ab, the fibrillar amyloid component, is a small molecule highly insoluble and resistant to degradation. Synthetic peptides homologous to Ab spontaneously polymerize in solution to form amyloid-like fibrils. However, a soluble form of Ab, i.e., sAb, has been identified in vivo as a normal component of different biological fluids. Our research focuses on the biological importance of the sAb molecule as the potential immediate precursor of the deposited Ab. We have identified apolipoprotein J (apoJ) as a major plasma and cerebrospinal fluid carrier protein for sAb. In addition, apoJ may well be responsible for the delivery of sAb through the blood-brain barrier. In vivo perfusion studies performed in guinea pigs indicate the existence of cerebrovascular permeability for synthetic Ab-apoJ complexes presumably mediated by the gp330/megalin, the receptor for apoJ. Longterm goals of our research are to understand the biochemical mechanism(s) of Ab amyloid deposition and the role of apoE and presenilins in the development of Alzheimer lesions.

 

 

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Professor, Department of Pathology

Professor, Department of Psychiatry

PhD from National University of Rosario

Murray, Christina E; Gami-Patel, Priya; Gkanatsiou, Eleni; Brinkmalm, Gunnar; Portelius, Erik; Wirths, Oliver; Heywood, Wendy; Blennow, Kaj; Ghiso, Jorge; Holton, Janice L; Mills, Kevin; Zetterberg, Henrik; Revesz, Tamas; Lashley, Tammaryn

Acta neuropathologica communications. 2018 07 20; 6(1):62

Cabrera, Erwin; Mathews, Paul; Mezhericher, Emiliya; Beach, Thomas G; Deng, Jingjing; Neubert, Thomas A; Rostagno, Agueda; Ghiso, Jorge

Biochimica & biophysica acta. 2018 Jan; 1864(1):208-225

Rostagno, Agueda; Neubert, Thomas A; Ghiso, Jorge

Methods in molecular biology. 2018 Jun; 1779:23-43

Protein folding disorders of the central nervous system

Ghiso, Jorge; Rostagno, Agueda

Protein folding disorders of the central nervous system. 2018. xix, 313 p. ; 24 cm (4158962)

Misfolding, aggregation, and amyloid formation : the dark side of proteins

Rostagno, Agueda; Ghiso, Jorge

Protein folding disorders of the central nervous system. 2018. p.1-32. (4158972)

Dave, Mandar; Islam, Abul B M M K; Jensen, Roderick V; Rostagno, Agueda; Ghiso, Jorge; Amin, Ashok R

Genomics, proteomics & bioinformatics. 2017 12; 15(6):339-351

Wirths, Oliver; Walter, Susanne; Kraus, Inga; Klafki, Hans W; Stazi, Martina; Oberstein, Timo J; Ghiso, Jorge; Wiltfang, Jens; Bayer, Thomas A; Weggen, Sascha

Alzheimer's research & therapy. 2017 Oct 04; 9(1):80

Wirths, O; Walter, S; Kraus, I; Klafki, H W; Stazi, M; Oberstein, T J; Ghiso, J; Wiltfang, J; Bayer, T A; Weggen, S

Alzheimer's research & therapy. 2017 Oct 04; 9(1):80