title: Lack of miRNA Misregulation at Early Pathological Stages in Drosophila Neurodegenerative Disease Models.
abstract: 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.
authors.affiliation: Laboratoire de Génétique du Stress et du Vieillissement, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC 4413, Université Paris Diderot Sorbonne Paris Cité, Paris, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Reinhardt
authors.forename: Sébastien
authors.initials: S
authors.lastname: Feuillette
authors.forename: Marlène
authors.initials: M
authors.lastname: Cassar
authors.forename: Céline
authors.initials: C
authors.lastname: Callens
authors.forename: Hélène
authors.initials: H
authors.lastname: Thomassin
authors.forename: Serge
authors.initials: S
authors.lastname: Birman
authors.forename: Magalie
authors.initials: M
authors.lastname: Lecourtois
authors.forename: Christophe
authors.initials: C
authors.lastname: Antoniewski
authors.forename: Hervé
authors.initials: H
authors.lastname: Tricoire
keywords: Parkinson disease; ataxia; deep sequencing; frontotemporal lobar degeneration; miRNA; neurodegenerative diseases; polyQ diseases