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Cited by 201Genetic Neurodegenerative DiseasesHeat shock proteins researchAmyotrophic Lateral Sclerosis Research

NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration

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Zhai, R. Grace, Zhang, Fan, Hiesinger, P. Robin, Cao, Yu, Haueter, Claire M., Bellen, Hugo J.·2008·Nature
DOI 10.1038/nature06721PMC PMC3150538
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Abstract

Neurodegeneration can be triggered by genetic or environmental factors. Although the precise cause is often unknown, many neurodegenerative diseases share common features such as protein aggregation and age dependence. Recent studies in Drosophila have uncovered protective effects of NAD synthase nicotinamide mononucleotide adenylyltransferase (NMNAT) against activity-induced neurodegeneration and injury-induced axonal degeneration. Here we show that NMNAT overexpression can also protect against spinocerebellar ataxia 1 (SCA1)-induced neurodegeneration, suggesting a general neuroprotective function of NMNAT. It protects against neurodegeneration partly through a proteasome-mediated pathway in a manner similar to heat-shock protein 70 (Hsp70). NMNAT displays chaperone function both in biochemical assays and cultured cells, and it shares significant structural similarity with known chaperones. Furthermore, it is upregulated in the brain upon overexpression of poly-glutamine expanded protein and recruited with the chaperone Hsp70 into protein aggregates. Our results implicate NMNAT as a stress-response protein that acts as a chaperone for neuronal maintenance and protection. Our studies provide an entry point for understanding how normal neurons maintain activity, and offer clues for the common mechanisms underlying different neurodegenerative conditions.

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Cited by

Sorted by citations

Authors
Zhai, R. G., Zhang, F., Hiesinger, P. R., Cao, Y., Haueter, C. M., & Bellen, H. J.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of Miami (US)
  • Baylor College of Medicine (US)
Corresponding author
  • Zhai, R. Grace
  • Bellen, Hugo J.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2008-03-16
Volume
452
Issue
7189
Pages
887-891
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature06721
PMC
PMC3150538
OpenAlex
W2032014604
Cited by
201
References
2
Citations by year
2026: 9 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 12 · 2020: 16 · 2019: 12 · 2018: 11 · 2017: 14 · 2016: 11 · 2015: 6 · 2014: 10 · 2013: 14 · 2012: 19
FWCI
7.07
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • University of Miami
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD024064)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
nicotinamide mononucleotide adenylyltransferase, chaperone activity, neurodegeneration, spinocerebellar ataxia type 1, protein aggregation, proteasome, HSP70, polyglutamine, stress response, neuroprotection, protein folding
MeSH terms
Ataxins, Ataxin-1, Animals, Brain, Chlorocebus aethiops, Disease Models, Animal, Drosophila, Humans, Nerve Degeneration, Nerve Tissue Proteins, Nicotinamide-Nucleotide Adenylyltransferase, Nuclear Proteins, Molecular Chaperones, HSP70 Heat-Shock Proteins, COS Cells, Neurodegenerative Diseases, Amide Synthases, Spinocerebellar Ataxias, Drosophila Proteins

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