Mapping of Italian research excellence in Neurodegenerative - Apre
Mapping of Italian research excellence in Neurodegenerative - Apre
Mapping of Italian research excellence in Neurodegenerative - Apre
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Nome Domenico Garozzo<br />
Contatti<br />
domenico.garozzo@cnr.it<br />
0957338259 3473576202<br />
Istituto/Dipartimento CNR ICTP Catania<br />
Via Gaifami 18 95125 Catania<br />
Proposta di ricerca<br />
Area di <strong>in</strong>teresse identificata<br />
F<strong>in</strong>anziamenti ricevuti<br />
Titolo progetto<br />
Glycomics<br />
CSF Glycomics <strong>in</strong> AD and other neurodegenerative diseases<br />
Ente f<strong>in</strong>anziatore MIUR (Italy)<br />
Durata progetto 3 years<br />
Abstract del progetto Prote<strong>in</strong> glycosylation is the most common among post-translational<br />
modifications (PTMs), which are key to the regulation <strong>of</strong> functional<br />
activities <strong>of</strong> prote<strong>in</strong>s. Quantitative and qualitative <strong>in</strong>formation about PTM<br />
stages <strong>of</strong> prote<strong>in</strong>s is crucial <strong>in</strong> the discovery <strong>of</strong> biomarkers <strong>of</strong> disease.<br />
Macroheterogeneity <strong>of</strong> prote<strong>in</strong> glycosylation depends on the extent <strong>of</strong><br />
glycosylation site occupancy while microheterogeneity refers to<br />
differences <strong>in</strong> the sugar cha<strong>in</strong> structures.<br />
Differences <strong>of</strong> prote<strong>in</strong> glycosylation may be <strong>in</strong>dicative <strong>of</strong> species<br />
synthesized <strong>in</strong> the central nervous system with respect to serum liverderived<br />
glyc<strong>of</strong>orms, [as already demonstrated for prote<strong>in</strong> Reel<strong>in</strong>, which is<br />
implicated <strong>in</strong> Alzheimer disease and <strong>in</strong> other neurodegenerative disorders<br />
(Botella-Lopez et al., 2006)]. Recent <strong>in</strong>sights <strong>in</strong>to neurodegenerative<br />
disorders caused by abnormal glycosylation <strong>of</strong> prote<strong>in</strong> Seip<strong>in</strong><br />
(Seip<strong>in</strong>opathy) show that modifications <strong>of</strong> Seip<strong>in</strong> glycosylation result <strong>in</strong><br />
improper fold<strong>in</strong>g lead<strong>in</strong>g to accumulation <strong>of</strong> the abnormal prote<strong>in</strong> <strong>in</strong> the<br />
endoplasmic reticulum, formation <strong>of</strong> ubiquit<strong>in</strong>ated <strong>in</strong>clusion, and<br />
activation <strong>of</strong> UPR (Ito and Suzuki, 2009).<br />
Prelim<strong>in</strong>ary <strong>in</strong>vestigations based on lect<strong>in</strong>-blott<strong>in</strong>g <strong>of</strong> CSF glycoprote<strong>in</strong>s<br />
revealed quantitative modifications <strong>in</strong> Alzheimer disease and altered<br />
glycosylation <strong>of</strong> CSF transferr<strong>in</strong> (Taniguchi et al. 2008). We apply mass<br />
spectrometry based glycomics <strong>of</strong> CSF as potential tool for to detect<br />
possible macro-and microheterogeneity <strong>of</strong> CSF glycoprote<strong>in</strong>s associated<br />
to Alzheimer disease. The availability <strong>of</strong> CSF depository from patients<br />
with AD and related disorders and established <strong>in</strong>teractions with cl<strong>in</strong>ical<br />
platforms will make possible to translate the results to cl<strong>in</strong>ical<br />
proteomics.<br />
The objective is to f<strong>in</strong>d out specific prote<strong>in</strong> posttranslational<br />
modifications related to glycosylation which <strong>in</strong> turn might be related to<br />
the analysed cellular phenomena associated to neurodegeneration.
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