NDLI: Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases

Content Provider	PubMed Central
Author	Anna, Sivachenko Gordon, Hannah B. Kimball, Suzanne S. Gavin, Erin J. Bonkowsky, Joshua L. Letsou, Anthea
Copyright Year	2016
Abstract	Debilitating neurodegenerative conditions with metabolic origins affect millions of individuals worldwide. Still, for most of these neurometabolic disorders there are neither cures nor disease-modifying therapies, and novel animal models are needed for elucidation of disease pathology and identification of potential therapeutic agents. To date, metabolic neurodegenerative disease has been modeled in animals with only limited success, in part because existing models constitute analyses of single mutants and have thus overlooked potential redundancy within metabolic gene pathways associated with disease. Here, we present the first analysis of a very-long-chain acyl-CoA synthetase (ACS) double mutant. We show that the Drosophila bubblegum (bgm) and double bubble (dbb) genes have overlapping functions, and that the consequences of double knockout of both bubblegum and double bubble in the fly brain are profound, affecting behavior and brain morphology, and providing the best paradigm to date for an animal model of adrenoleukodystrophy (ALD), a fatal childhood neurodegenerative disease associated with the accumulation of very-long-chain fatty acids. Using this more fully penetrant model of disease to interrogate brain morphology at the level of electron microscopy, we show that dysregulation of fatty acid metabolism via disruption of ACS function in vivo is causal of neurodegenerative pathologies that are evident in both neuronal cells and their supporting cell populations, and leads ultimately to lytic cell death in affected areas of the brain. Finally, in an extension of our model system to the study of human disease, we describe our identification of an individual with leukodystrophy who harbors a rare mutation in SLC27a6 (encoding a very-long-chain ACS), a human homolog of bgm and dbb.
Related Links	http://dx.doi.org/10.1242/dmm.022244
Ending Page	387
Page Count	11
Starting Page	377
File Format	PDF
ISSN	17548403
e-ISSN	17548411
Journal	Disease Models & Mechanisms
Issue Number	4
Volume Number	9
Language	English
Publisher	The Company of Biologists Ltd
Publisher Date	2016-04-01
Access Restriction	Open
Rights Holder	The Company of Biologists Ltd
Subject Keyword	Immunology and Microbiology (miscellaneous) Biochemistry, Genetics and Molecular Biology(all) Medicine (miscellaneous) Neuroscience (miscellaneous) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Synaptic roles for phosphomannomutase type 2 in a new Drosophila congenital disorder of glycosylation disease model

Absence of the Cdk5 activator p35 causes adult-onset neurodegeneration in the central brain of Drosophila

Synaptic abnormalities in a Drosophila model of Alzheimer’s disease

A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders

A Drosophila model to investigate the neurotoxic side effects of radiation exposure

A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

Drosophila melanogaster as a model for human intestinal infection and pathology

The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease

Drosophila: a model for studying genetic and molecular aspects of haematopoiesis and associated leukaemias

Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases

Similar Documents

Synaptic roles for phosphomannomutase type 2 in a new Drosophila congenital disorder of glycosylation disease model

Absence of the Cdk5 activator p35 causes adult-onset neurodegeneration in the central brain of Drosophila

Synaptic abnormalities in a Drosophila model of Alzheimer’s disease

A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders

A Drosophila model to investigate the neurotoxic side effects of radiation exposure

A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

Drosophila melanogaster as a model for human intestinal infection and pathology

The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease

Drosophila: a model for studying genetic and molecular aspects of haematopoiesis and associated leukaemias

Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases