Publications

Authors:

Bossolasco, Patrizia; Cimini, Sara; Maderna, Emanuela; Bardelli, Donatella; Canafoglia, Laura; Cavallaro, Tiziana; Ricci, Martina; Silani, Vincenzo; Marucci, Gianluca; Rossi, Giacomina

Title:

GRN-/- iPSC-derived cortical neurons recapitulate the pathological findings of both frontotemporal lobar degeneration and neuronal ceroidolipofuscinosis

Year:

2022

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

NEUROBIOLOGY OF DISEASE

ISSN of journal:

0969-9961

N° Volume:

175

Number or Folder:

105891

:

Academic Press Incorporated:6277 Sea Harbor Drive:Orlando, FL 32887:(800)543-9534, (407)345-4100, EMAIL: ap@acad.com, INTERNET: http://www.idealibrary.com, Fax: (407)352-3445

Page numbers:

1-11

Keyword:

Cortical neurons; Fingerprints; Frontotemporal lobar degeneration; Induced pluripotent stem cells; Lysosomes; Neuronal ceroidolipofuscinosis; Progranulin; TDP-43

Short description of contents:

Heterozygous mutations in the gene coding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) while homozygous mutations are linked to neuronal ceroidolipofuscinosis (NCL). While both FTLD/NCL pathological hallmarks were mostly investigated in heterozygous GRN+/- brain tissue or iPSC-derived neurons, data from homozygous GRN-/- condition are scarce, being limited to a postmortem brain tissue from a single case. Indeed, homozygous GRN-/- is an extremely rare condition reported in very few cases. Our aim was to investigate pathological phenotypes associated to both FTLD and NCL in iPSC-derived cortical neurons from a GRN-/- patient affected by NCL. iPSCs were generated from peripheral blood of a GRN wt healthy donor and a GRN-/- patient and subsequently differentiated into cortical neurons. Several pathological changes were investigated, by means of immunocytochemical, biochemical and ultrastructural analyses. GRN-/- patient-derived cortical neurons displayed both TDP-43 and phospho-TDP-43 mislocalization, enlarged autofluorescent lysosomes and electron-dense vesicles containing storage material with granular, curvilinear and fingerprints profiles. In addition, different patterns in the expression of TDP-43, caspase 3 and cleaved caspase 3 were observed by biochemical analysis at different time points of cortical differentiation. At variance with previous findings, the present data highlight the existence of both FTLD- and NCL-linked pathological features in GRN-/- iPSC-derived cortical neurons from a NCL patient. They also suggest an evolution in the appearance of these features: firstly, FTLD-related TDP-43 alterations and initial NCL storage materials were detected; afterwards, mainly well-shaped NCL storage materials were present, while some FTLD features were not observed anymore.

Web page:

https://doi.org/10.1016/j.nbd.2022.105891

Product ID:

130215

Handle IRIS:

11562/1078889

Last Modified:

February 23, 2023

Bibliographic citation:

Bossolasco, Patrizia; Cimini, Sara; Maderna, Emanuela; Bardelli, Donatella; Canafoglia, Laura; Cavallaro, Tiziana; Ricci, Martina; Silani, Vincenzo; Marucci, Gianluca; Rossi, Giacomina, GRN-/- iPSC-derived cortical neurons recapitulate the pathological findings of both frontotemporal lobar degeneration and neuronal ceroidolipofuscinosis «NEUROBIOLOGY OF DISEASE» , vol. 175 , n. 105891 , 2022 , pp. 1-11

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo