Lack of miRNA Misregulation at Early Pathological Stages in Drosophila Neurodegenerative Disease Models

Anita Reinhardt (1) , Sébastien Feuillette (2) , Marlène Cassar (3) , Céline Callens (3) , Hélène Thomassin (4) , Serge Birman (3) , Magalie Lecourtois (2) , Christophe Antoniewski (4) , Hérvé Tricoire (1)

1 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
2 GMFC - Génétique du cancer et des maladies neuropsychiatriques
3 Laboratoire de Neurobiologie
4 LBD - Laboratoire de Biologie du Développement

Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80–84 year-old Europeans) or Parkinson disease (PD, 1.4% prevalence for >55 years old) share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence) and frontotemporal lobar degeneration (FTLD, 0.02% prevalence), a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs (miRNAs), a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases.The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias, and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs.To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for seven diseases (PD, 3 FTLD, 3 dominant ataxias) that recapitulate many features of the human diseases.We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons.We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non-coding CAG repeat RNAs (sCAG) in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

Mots clés: miRNA; neurodegenerative diseases; ataxia; frontotemporal lobar degeneration; Parkinson disease; polyQ diseases; deep sequencing

Domaines: Neurosciences [q-bio.NC]

Anita Reinhardt, Sébastien Feuillette, Marlène Cassar, Céline Callens, Hélène Thomassin, et al.. Lack of miRNA Misregulation at Early Pathological Stages in Drosophila Neurodegenerative Disease Models. Frontiers in Genetics, 2012, 3 (226), 14 p. ⟨10.3389/fgene.2012.00226⟩. ⟨hal-02331191⟩