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PMID: 14676324 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Loss of poly(ADP-ribose) glycohydrolase causes progressive neurodegeneration in Drosophila melanogaster.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 1 ·2004-01-06 ·Pages 82-6

Hanai S, Kanai M, Ohashi S, Okamoto K, Yamada M, Takahashi H, Miwa M

Abstract

Poly(ADP-ribosyl)ation has been suggested to be involved in regulation of DNA repair, transcription, centrosome duplication, and chromosome stability. However, the regulation of degradation of poly(ADP-ribose) and its significance are not well understood. Here we report a loss-of-function mutant Drosophila with regard to poly(ADP-ribose) glycohydrolase, a major hydrolyzing enzyme of poly(ADP-ribose). The mutant lacks the conserved catalytic domain of poly(ADP-ribose) glycohydrolase, and exhibits lethality in the larval stages at the normal development temperature of 25 degrees C. However, one-fourth of the mutants progress to the adult stage at 29 degrees C but showed progressive neurodegeneration with reduced locomotor activity and a short lifespan. In association with this, extensive accumulation of poly(ADP-ribose) could be detected in the central nervous system. These results suggest that poly(ADP-ribose) metabolism is required for maintenance of the normal function of neuronal cells. The phenotypes observed in the parg mutant might be useful to understand neurodegenerative conditions such as the Alzheimer's and Parkinson's diseases that are caused by abnormal accumulation of substances in nervous tissue.

MeSH Terms
Animals Base Sequence Brain/ultrastructure DNA/genetics Drosophila melanogaster/enzymology,genetics,growth & development Female Genes, Insect Glycoside Hydrolases/deficiency,genetics,physiology Humans Male Microscopy, Electron Mutation Nerve Degeneration/enzymology,genetics,pathology Phenotype Temperature
Chemicals
DNA Glycoside Hydrolases poly ADP-ribose glycohydrolase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hanai Shuji
Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Kanai Masayuki
Ohashi Sayaka
Okamoto Keiji
Yamada Mitsunori
Takahashi Hitoshi
Miwa Masanao
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.2237114100
Published
2004-01-06
Epub
2003-00-15
Pages
82-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC314142
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.2237114100 PMC Full Text View journal details
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