An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain

Genetics
Jongkyun KangJie Shen

Abstract

Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin (Psn) and Nicastrin (Nct) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct, neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4...Continue Reading

References

Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·G D Schellenberg
Feb 1, 1996·Genome Génome / Conseil National De Recherches Canada·K Gustafson, G L Boulianne
Feb 10, 1997·Neuroreport·C S Hong, E H Koo
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·W SongB A Yankner
Nov 11, 1999·Genes & Development·D B DonovielA Bernstein
Apr 4, 2000·Nature·M B Feany, W W Bender
Jan 10, 2002·Developmental Cell·Hernán López-Schier, Daniel St Johnston
Dec 6, 2003·Science·Sean E McGuireRonald L Davis
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ruiben FengJoe Z Tsien
Sep 4, 2004·The Journal of Biological Chemistry·Vassilios BeglopoulosJie Shen
Sep 8, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Tianyi ZhangFrancesca Pignoni
Apr 22, 2006·Brain Research·Van NguyenRichard Rozmahel
May 23, 2006·Current Biology : CB·Glen A SeidnerMark E Fortini
Dec 2, 2006·BMC Bioinformatics·Jean-Philippe VertYves Vandenbrouck
Dec 19, 2006·The Journal of Clinical Investigation·Dora Dias-SantagataMel B Feany
Jan 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jie Shen, Raymond J Kelleher
Jun 15, 2007·Developmental Neurobiology·David KnightGabrielle L Boulianne
Jan 10, 2008·Molecular Neurodegeneration·Woo-Young Kim, Jie Shen
Feb 26, 2009·Genesis : the Journal of Genetics and Development·Diana L van de HoefGabrielle L Boulianne
Jun 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Katsuhiko TabuchiJie Shen
Jul 16, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sean M J McBrideThomas A Jongens

❮ Previous
Next ❯

Citations

Nov 17, 2017·Proceedings of the National Academy of Sciences of the United States of America·Hirotaka Watanabe, Jie Shen
Jul 8, 2020·Biomolecules·Jose L SalazarShinya Yamamoto
Dec 12, 2020·Molecular Neurodegeneration·Jongkyun Kang, Jie Shen
Dec 15, 2021·PLoS Genetics·Jose L SalazarShinya Yamamoto

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.