Titre :

Reduced tau protein expression is associated with frontotemporal degeneration with progranulin mutation

Auteur(s) :

Papegaey, Anthony [Auteur]
Eddarkaoui, Sabiha [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Deramecourt, Vincent [Auteur]

Lille Neurosciences & Cognition (LilNCog) - U 1172
Fernandez-Gomez, Francisco-Jose [Auteur]
Pantano, Pierre [Auteur]
Obriot, Helene [Auteur]
Machala, Camille [Auteur]
Anquetil, Vincent [Auteur]
Camuzat, Agnes [Auteur]
Brice, Alexis [Auteur]
Maurage, Claude-Alain [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Le Ber, Isabelle [Auteur]
Duyckaerts, Charles [Auteur]
Buee, Luc [Auteur]


Sergeant, Nicolas [Auteur]


Buee-Scherrer, Valerie [Auteur]

Titre de la revue :

Acta neuropathologica communications

Nom court de la revue :

Acta Neuropathol. Commun.

Numéro :

4

Date de publication :

2016-07-19

ISSN :

2051-5960

Mot(s)-clé(s) en anglais :

Tau protein
Frontotemporal lobar degeneration
Astrogliosis
Synaptic impairment
Progranulin

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Reduction of Tau protein expression was described in 2003 by Zhukareva et al. in a variant of frontotemporal lobar degeneration (FTLD) referred to as diagnosis of dementia lacking distinctive histopathology, then re-classified ...
Lire la suite >Reduction of Tau protein expression was described in 2003 by Zhukareva et al. in a variant of frontotemporal lobar degeneration (FTLD) referred to as diagnosis of dementia lacking distinctive histopathology, then re-classified as FTLD with ubiquitin inclusions. However, the analysis of Tau expression in FTLD has not been reconsidered since then. Knowledge of the molecular basis of protein aggregates and genes that are mutated in the FTLD spectrum would enable to determine whether the "Tau-less" is a separate pathological entity or if it belongs to an existing subclass of FTLD. To address this question, we have analyzed Tau expression in the frontal brain areas from control, Alzheimer's disease and FTLD cases, including FTLD- Tau (MAPT), FTLD-TDP (sporadic, FTLD-TDP-GRN, FTLD-TDP-C9ORF72) and sporadic FTLD-FUS, using western blot and 2D-DIGE (Two-Dimensional fluorescence Difference Gel Electrophoresis) approaches. Surprisingly, we found that most of the FTLD-TDP-GRN brains are characterized by a huge reduction of Tau protein expression without any decrease in Tau mRNA levels. Interestingly, only cases affected by point mutations, rather than cases with total deletion of one GRN allele, seem to be affected by this reduction of Tau protein expression. Moreover, proteomic analysis highlighted correlations between reduced Tau protein level, synaptic impairment and massive reactive astrogliosis in these FTLD-GRN cases. Consistent with a recent study, our data also bring new insights regarding the role of progranulin in neurodegeneration by suggesting its involvement in lysosome and synaptic regulation. Together, our results demonstrate a strong association between progranulin deficiency and reduction of Tau protein expression that could lead to severe neuronal and glial dysfunctions. Our study also indicates that this FTLD-TDP-GRN subgroup could be part as a distinct entity of FTLD classification.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2019-11-27T14:28:51Z