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Reprogramming neurodegeneration in the big data era.

Lujia Zhou1, Patrik Verstreken1

  • 1VIB-KU Leuven Center for Brain & Disease Research, Leuven 3000, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium.

Current Opinion in Neurobiology
|January 15, 2018
PubMed
Summary
This summary is machine-generated.

Genome-wide association studies (GWAS) identified genetic risks for Alzheimer's disease (AD) and Parkinson's disease (PD). Pluripotent stem cell (PSC) models combined with genome-wide approaches offer new insights into disease mechanisms.

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Area of Science:

  • Neuroscience
  • Genetics
  • Stem Cell Biology

Background:

  • Genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD).
  • Deciphering the functional consequences of these GWAS findings is challenging due to the low penetrance and non-coding nature of many identified variants, coupled with a lack of suitable human model systems.
  • Understanding the genetic underpinnings of neurodegenerative diseases is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To review and discuss the utility of pluripotent stem cell (PSC) technologies for studying genetic risk variants in Alzheimer's disease (AD) and Parkinson's disease (PD).
  • To highlight how integrated studies combining PSC-derived models with genome-wide approaches can elucidate the functional consequences of GWAS findings.
  • To explore the potential of these integrated approaches in uncovering novel mechanistic insights into AD and PD pathogenesis.

Main Methods:

  • Utilizing pluripotent stem cell (PSC) technologies to generate human neurons and microglia relevant to AD and PD.
  • Applying advanced whole-genome RNA-sequencing and epigenome mapping techniques to PSC-derived disease models.
  • Integrating data from GWAS with molecular and cellular data from PSC models for comprehensive analysis.

Main Results:

  • PSC technologies provide powerful platforms for the molecular phenotyping of genetic variants associated with AD and PD.
  • Genome-wide approaches, including RNA-sequencing and epigenome mapping, enable unbiased investigation of molecular alterations in PSC-derived models.
  • Integrated studies using PSCs and genome-wide data facilitate the study of low penetrance and non-coding genetic variants.

Conclusions:

  • Integrated studies combining PSC technologies and genome-wide approaches offer unprecedented opportunities to unravel the pathogenesis of AD and PD.
  • These integrated strategies are essential for deciphering the functional impact of GWAS-identified genetic risk variants.
  • This approach holds significant promise for advancing our understanding of neurodegenerative disease mechanisms and identifying potential therapeutic targets.