PMID- 29440694
OWN - NLM
STAT- MEDLINE
DCOM- 20190912
LR  - 20190912
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Feb 13
TI  - Mutations in the Drosophila homolog of human PLA2G6 give rise to age-dependent 
      loss of psychomotor activity and neurodegeneration.
PG  - 2939
LID - 10.1038/s41598-018-21343-8 [doi]
LID - 2939
AB  - Infantile neuroaxonal dystrophy (INAD) is a fatal neurodegenerative disorder that 
      typically begins within the first few years of life and leads to progressive 
      impairment of movement and cognition. Several years ago, it was shown that >80% 
      of patients with INAD have mutations in the phospholipase gene, PLA2G6. 
      Interestingly, mutations in PLA2G6 are also causative in two other related 
      neurodegenerative diseases, atypical neuroaxonal dystrophy and 
      Dystonia-parkinsonism. While all three disorders give rise to similar defects in 
      movement and cognition, some defects are unique to a specific disorder. At 
      present, the cellular mechanisms underlying PLA2G6-associated neuropathology are 
      poorly understood and there is no cure or treatment that can delay disease 
      progression. Here, we show that loss of iPLA2-VIA, the Drosophila homolog of 
      PLA2G6, gives rise to age-dependent defects in climbing and spontaneous 
      locomotion. Moreover, using a newly developed assay, we show that iPLA2-VIA 
      mutants also display impairments in fine-tune motor movements, motor coordination 
      and psychomotor learning, which are distinct features of PLA2G6-associated 
      disease in humans. Finally, we show that iPLA2-VIA mutants exhibit increased 
      sensitivity to oxidative stress, progressive neurodegeneration and a severely 
      reduced lifespan. Altogether, these data demonstrate that Drosophila iPLA2-VIA 
      mutants provide a useful model to study human PLA2G6-associated 
      neurodegeneration.
FAU - Iliadi, Konstantin G
AU  - Iliadi KG
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Toronto, Ontario M5G 1L7, Canada. iliadi@sickkids.ca.
FAU - Gluscencova, Oxana B
AU  - Gluscencova OB
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Toronto, Ontario M5G 1L7, Canada.
FAU - Iliadi, Natalia
AU  - Iliadi N
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Toronto, Ontario M5G 1L7, Canada.
FAU - Boulianne, Gabrielle L
AU  - Boulianne GL
AUID- ORCID: 0000-0002-2964-2344
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Toronto, Ontario M5G 1L7, Canada. gboul@sickkids.ca.
AD  - Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 
      1A8, Canada. gboul@sickkids.ca.
LA  - eng
GR  - PJT15063/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180213
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Drosophila Proteins)
RN  - EC 3.1.1.4 (Group X Phospholipases A2)
RN  - EC 3.1.1.4 (iPLA2-VIA protein, Drosophila)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Aging/genetics
MH  - Alleles
MH  - Animals
MH  - Calcium/metabolism
MH  - Drosophila Proteins/*genetics/metabolism
MH  - *Drosophila melanogaster
MH  - Female
MH  - Group X Phospholipases A2/*genetics/metabolism
MH  - Humans
MH  - Longevity
MH  - Male
MH  - Motor Activity/*genetics
MH  - *Mutation
MH  - Neurodegenerative Diseases/*genetics/metabolism/*physiopathology
MH  - Oxidative Stress/genetics
MH  - *Sequence Homology, Nucleic Acid
PMC - PMC5811537
COIS- The authors declare no competing interests.
EDAT- 2018/02/15 06:00
MHDA- 2019/09/13 06:00
PMCR- 2018/02/13
CRDT- 2018/02/15 06:00
PHST- 2017/09/18 00:00 [received]
PHST- 2017/12/20 00:00 [accepted]
PHST- 2018/02/15 06:00 [entrez]
PHST- 2018/02/15 06:00 [pubmed]
PHST- 2019/09/13 06:00 [medline]
PHST- 2018/02/13 00:00 [pmc-release]
AID - 10.1038/s41598-018-21343-8 [pii]
AID - 21343 [pii]
AID - 10.1038/s41598-018-21343-8 [doi]
PST - epublish
SO  - Sci Rep. 2018 Feb 13;8(1):2939. doi: 10.1038/s41598-018-21343-8.