Laboratory of chemical biology of neurodegeneration
Laboratory of chemical biology of neurodegeneration
Coordinator
Name: Cristina Cecchi
Position: Associate Professor of Biochemistry
e-mail: cristina.cecchi@unifi.it
Telephone number: 0039 055-2751222
Brief Biographical sketch of the Coordinator
1991 M.Sc. degree in Biological Sciences at the University of Florence.
1995 Specialisation degree of Biochemistry and Clinical Chemistry at the Faculty of Medicine and Surgery of the University of Florence.
2001 PhD degree (D.Phil) in Biochemistry at the University of Florence.
In 2015 she obtained the National Academic Qualification as Full Professor (05/E1)
Member of the Scientific Board the Doctorate/Phd Program in
Biomedical Sciences
Memeber of the following Scientific Societies
Italian Society of Biochemistry (SIB)
Member of editorial board of the following Journals
International Journal of Molecular Sciences, Journal of Alzheimer’s Disease
Research Team
Roberta Cascella, PhD, Assistant Professor
Alessandra Bigi, PhD, Post-Doc
Current research interest
- Study of the relationship between structure and toxicity of protein aggregates associated with Alzheimer’s, Parkinson’s diseases and amyotrophic lateral sclerosis (ALS);
- Study of the protective role of molecular chaperones, glutathione thioesters, and aminosterols against protein aggregates toxicity;
- Study of the effect of membrane lipid components on aggregates toxicity.
The experimental work involves the use of different animal and cellular models including C. elegans nematodes, rat models, and different types of cultured cells such as primary cultures (hippocampal and cortical neurons from rat brains, skin fibroblasts from familial Alzheimer’s disease patients, human iPSC-derived neurons) and immortalized cell lines (human and murine neuroblastoma cells, hybrid motor neuron-like cells). Projects involve use of specific protocols to assess cell viability, oxidative stress and calcium homeostasis mainly by confocal microscopy and FACS techniques.
Keywords
Neurodegeneration, Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis, protein aggregation, amyloid, toxic oligomers, protein misfolding, amyloid-β peptide, α-synuclein, TDP-43.
Current/recent sources of funding
- FAS-salute Regione Toscana (SUPREMAL, PRAMA);
- FFABR;
- AriSLA;
- Fondi di Ateneo;
- Fondi Dip. Eccellenza (Gender medicine);
- Fondazione Cassa di Risparmio di Pistoia e Pescia;
- Cassa di Risparmio di Firenze.
10 best publications of the last 5 years
- Limbocker R, Mannini B, Ruggeri FS, Cascella R, Xu CK, Perni M, Chia S, Chen SW, Habchi J, Bigi A, Kreiser RP, Wright AK, Albright JA, Kartanas T, Kumita JR, Cremades N, Zasloff M, Cecchi C, Knowles TPJ, Chiti F, Vendruscolo M, Dobson CM. Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism. Commun Biol. 2020; 3: 435.
- Banchelli M, Cascella R, D'Andrea C, Cabaj L, Osticioli I, Ciofini D, Li SM, Skupie´n K, de Angelis M, Siano S, Cecchi C, Pini R, La Penna G, Chiti F, Matteini P. Nanoscopic insights into the surface conformation of neurotoxic amyloid b oligomers. RSC ADV. 2020; 10: 21907-21913.
- Cascella R., Fani G, Bigi A, Chiti F, Cecchi C. Partial failure of proteostasis systems counteracting TDP-43 aggregates in neurodegenerative diseases. Int J Mol Sci. 2019; 20: 3685.
- Limbocker R, Chia S, Ruggeri FS, Perni M, Cascella R, Heller GT, Meisl G, Mannini B, Habchi J, Michaels TCT, Challa PK, Ahn M, Casford ST, Fernando N, Xu CK, Kloss ND, Cohen SIA, Kumita JR, Cecchi C, Zasloff M, Linse S, Knowles TPJ, Chiti F, Vendruscolo M. Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes. Nat Commun. 2019; 10: 225.
- Perni M, Flagmeier P, Limbocker R, Cascella R, Aprile FA, Galvagnion C, Heller GT, Meisl G, Chen SW, Kumita JR, Challa PK, Kirkegaard JB, Cohen SIA, Mannini B, Barbut D, Nollen EAA, Cecchi C, Cremades N, Knowles TPJ, Chiti F, Zasloff M, Vendruscolo M, Dobson CM. Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine. ACS Chem Biol. 2018; 13: 2308.
- Fusco G, Chen SW, Williamson PTF, Cascella R, Perni M, Jarvis JA, Cecchi C, Vendruscolo M, Chiti F, Cremades N, Ying L, Dobson CM, De Simone A. Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers. Science 2017; 358: 1440.
- Perni M, Galvagnion C, Maltsev A, Meisl G, Müller MBD, Challa PK, Kirkegaard J, Flagmeier P, Cohen SIA, Cascella R, Chen S, Limboker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EAA, Knowles TPJ, Vendruscolo M, Bax A, Zasloff M, Dobson CM. A natural product inhibits the initiation of a-synuclein aggregation and suppresses its toxicity. Proc Natl Acad Sci U S A. 2017; 114: E1009-E1017.
- Cascella R, Evangelisti E, Bigi A, Becatti M, Fiorillo C, Stefani M, Chiti F, Cecchi C. Soluble Oligomers Require a Ganglioside to Trigger Neuronal Calcium Overload. J Alzheimers Dis. 2017; 60: 923-938.
- Cascella R, Fani G, Capitini C, Rusmini P, Poletti A, Cecchi C, Chiti F. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy. FASEB J. 2017, 31: 5609.
- Cascella R, Capitini C, Fani G, Dobson CM, Cecchi C, Chiti F. Quantification of the relative contributions of loss-of-function and gain-of-function mechanisms in TDP-43 proteinopathies. J Biol Chem. 2016; 291: 19437-19448.
- Evangelisti E, Cascella R, Becatti M, Marrazza G, Dobson CM, Chiti F, Stefani M, Cecchi C. Binding affinity of amyloid oligomers to cellular membranes is a generic indicator of cellular dysfunction in protein misfolding diseases. Sci Rep. 2016; 6: 32721.
Previous research experiences
- European Project Seventh Framework Programme of European Commission (FP7) (2008-2011) – Title: NANO-MUBIOP – Enhanced Sensitivity Nanotechnology-based Multiplex Bioassay Platform for diagnostic applications.
- PRIN 2008 – Title: “Approccio integrato alla relazione esistente tra Aß, danno ossidativo, complesso proteasomale ed autofagia. Effetto di molecole neuroprotettive”.
- PRIN 2005 – Basi molecolari della citotossicità indotta dai diversi stati di aggregazione di beta amiloide: studio multidisciplinare in vitro, su colture cellulari e su modello animale.
- Regione Toscana (POR CRO FSE 2007-2013) – Title: “Studio della relazione fra struttura e capacità citotossica di proteine coinvolte nelle malattie da deposizione proteica: sviluppo di un test diagnostico”.
Main scientific contributions
- Identification of the cytotoxic pathways associated with protein misfolded diseases;
- Identification of the protective effects of molecular chaperones, glutathione thioesters, and aminosterols as therapeutic strategy for Alzheimer’s, Parkinson’s Diseases and ALS.
Collaborations
- Michele Vendruscolo, Department of Chemistry, University of Cambridge;
- Mark Wilson, School of Biological Sciences, University of Wollongong, Australia;
- Joel Buxbaum, Department of Molecular and Experimental Medicine, The Scripps Research Institute;
- Nunilo Cremades, Institute for Biocomputation and Fisics of Complex system, Universitat de Saragoza, Spain;
- Hassan Ramshini, Department of Biology, Payam e Noor University, Branch of Sabzevar, Iran;
- Neville Vassallo, Department of Physiology & Biochemistry, University of Malta, Tal-Qroqq, Malta;
- Annalisa Relini, Dipartimento di Fisica, Università di Genova, Italy;
- Angelo Poletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Italy;
- Daniela Marasco, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Italy;
- Alfonso De Simone, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II;
- Serena Carra, Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università degli Studi di Modena e Reggio Emilia, Italy;
- Paolo Matteini, Istituto di Fisica Applicata, Consiglio Nazionale delle Ricerche, Sesto Fiorentino, Italy.
Ultimo aggiornamento
01.12.2021