PMID- 27141409
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160504
LR  - 20201001
IS  - 2167-5511 (Print)
IS  - 2167-5511 (Electronic)
IS  - 2167-5511 (Linking)
VI  - 4
IP  - 1
DP  - 2016
TI  - Mitochondrial dysfunction and defects in lipid homeostasis as therapeutic targets 
      in neurodegeneration with brain iron accumulation.
PG  - e1128616
LID - 10.1080/21675511.2015.1128616 [doi]
LID - e1128616
AB  - The PLA2G6 gene encodes a group VIA calcium independent phospholipase A2 
      (iPLA2beta), which hydrolyses glycerophospholipids to release fatty acids and 
      lysophospholipids. Mutations in PLA2G6 are associated with a number of 
      neurodegenerative disorders including neurodegeneration with brain iron 
      accumulation (NBIA), infantile neuroaxonal dystrophy (INAD), and dystonia 
      parkinsonism, collectively known as PLA2G6-associated neurodegeneration (PLAN). 
      Recently Kinghorn et al. demonstrated in Drosophila and PLA2G6 mutant fibroblasts 
      that loss of normal PLA2G6 activity is associated with mitochondrial dysfunction 
      and mitochondrial lipid peroxidation. Furthermore, they were able to show the 
      beneficial effects of deuterated polyunsaturated fatty acids (D-PUFAs), which 
      reduce lipid peroxidation. D-PUFAs were able to rescue the locomotor deficits of 
      flies lacking the fly ortholog of PLA2G6 (iPLA2-VIA), as well as the 
      mitochondrial abnormalities in PLA2G6 mutant fibroblasts. This work demonstrated 
      that the iPLA2-VIA knockout fly is a useful organism to dissect the mechanisms of 
      pathogenesis of PLAN, and that further investigation is required to determine the 
      therapeutic potential of D-PUFAs in patients with PLA2G6 mutations. The fruit fly 
      has also been used to study some of the other genetic causes of NBIA, and here we 
      also describe what is known about the mechanisms of pathogenesis of these NBIA 
      variants. Mitochondrial dysfunction, defects in lipid metabolism, as well as 
      defective Coenzyme A (CoA) biosynthesis, have all been implicated in some genetic 
      forms of NBIA, including PANK2, CoASY, C12orf19 and FA2H.
FAU - Kinghorn, Kerri J
AU  - Kinghorn KJ
AD  - Institute of Healthy Ageing and Department of Genetics, Environment and 
      Evolution, University College London, London, UK; Institute of Neurology, 
      University College London, Queen Square, London, UK.
FAU - Castillo-Quan, Jorge Ivan
AU  - Castillo-Quan JI
AD  - Institute of Healthy Ageing and Department of Genetics, Environment and 
      Evolution, University College London, London, UK; Institute of Neurology, 
      University College London, Queen Square, London, UK.
LA  - eng
PT  - Journal Article
DEP - 20160125
PL  - United States
TA  - Rare Dis
JT  - Rare diseases (Austin, Tex.)
JID - 101603407
EIN - doi: 10.1093/brain/awv132
PMC - PMC4838319
OTO - NOTNLM
OT  - PLA2G6
OT  - deuterated polyunsaturated fatty acids
OT  - drosophila
OT  - lipid peroxidation
OT  - neurodegeneration with brain iron accumulation
EDAT- 2016/05/04 06:00
MHDA- 2016/05/04 06:01
PMCR- 2016/01/25
CRDT- 2016/05/04 06:00
PHST- 2015/07/13 00:00 [received]
PHST- 2015/11/11 00:00 [revised]
PHST- 2015/12/01 00:00 [accepted]
PHST- 2016/05/04 06:00 [entrez]
PHST- 2016/05/04 06:00 [pubmed]
PHST- 2016/05/04 06:01 [medline]
PHST- 2016/01/25 00:00 [pmc-release]
AID - 1128616 [pii]
AID - 10.1080/21675511.2015.1128616 [doi]
PST - epublish
SO  - Rare Dis. 2016 Jan 25;4(1):e1128616. doi: 10.1080/21675511.2015.1128616. 
      eCollection 2016.