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A systems-biology approach connects aging mechanisms with Alzheimer's disease pathogenesis.
Leventhal, Matthew J; Zanella, Camila A; Kang, Byunguk; Peng, Jiajie; Gritsch, David; Liao, Zhixiang; Bukhari, Hassan; Wang, Tao; Pao, Ping-Chieh; Danquah, Serwah; Benetatos, Joseph; Nehme, Ralda; Farhi, Samouil; Tsai, Li-Huei; Dong, Xianjun; Scherzer, Clemens R; Feany, Mel B; Fraenkel, Ernest.
Afiliación
  • Leventhal MJ; MIT Ph.D. Program in Computational and Systems Biology, Cambridge, MA, USA.
  • Zanella CA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Kang B; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Peng J; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Gritsch D; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Liao Z; Spatial Technology Platform, Broad Institute of Harvard and MIT, Cambridge, MA USA.
  • Bukhari H; Precision Neurology Program, Brigham and Women's Hospital and Harvard Medical school, Boston, MA, USA.
  • Wang T; APDA Center for Advanced Parkinson's Disease Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Pao PC; Precision Neurology Program, Brigham and Women's Hospital and Harvard Medical school, Boston, MA, USA.
  • Danquah S; APDA Center for Advanced Parkinson's Disease Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Benetatos J; Precision Neurology Program, Brigham and Women's Hospital and Harvard Medical school, Boston, MA, USA.
  • Nehme R; APDA Center for Advanced Parkinson's Disease Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Farhi S; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Tsai LH; Precision Neurology Program, Brigham and Women's Hospital and Harvard Medical school, Boston, MA, USA.
  • Dong X; APDA Center for Advanced Parkinson's Disease Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Scherzer CR; Present address: School of Computer Science, Northwestern Polytechnical University, Xi'an, China.
  • Feany MB; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Fraenkel E; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
bioRxiv ; 2024 Mar 17.
Article en En | MEDLINE | ID: mdl-38559190
ABSTRACT
Age is the strongest risk factor for developing Alzheimer's disease, the most common neurodegenerative disorder. However, the mechanisms connecting advancing age to neurodegeneration in Alzheimer's disease are incompletely understood. We conducted an unbiased, genome-scale, forward genetic screen for age-associated neurodegeneration in Drosophila to identify the underlying biological processes required for maintenance of aging neurons. To connect genetic screen hits to Alzheimer's disease pathways, we measured proteomics, phosphoproteomics, and metabolomics in Drosophila models of Alzheimer's disease. We further identified Alzheimer's disease human genetic variants that modify expression in disease-vulnerable neurons. Through multi-omic, multi-species network integration of these data, we identified relationships between screen hits and tau-mediated neurotoxicity. Furthermore, we computationally and experimentally identified relationships between screen hits and DNA damage in Drosophila and human iPSC-derived neural progenitor cells. Our work identifies candidate pathways that could be targeted to attenuate the effects of age on neurodegeneration and Alzheimer's disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos