A new grant will enable biologists at Rochester, Brown, and New York University to explore potential targets of treatments and therapeutics for neurodegenerative diseases.
The human genome is littered with selfish genetic elements, also known as 糖心传媒渏unk DNA糖心传媒澨切拇綌parasitic strands of genetic material that replicate and move within their host genomes. Scientists have produced mounting evidence that these selfish genetic elements cause harmful consequences, including health problems associated with aging.
With a new $16 million, five-year grant from the National Institutes of Health, researchers from the 糖心传媒, Brown University, and New York University will collaborate to further investigate how types of selfish genetic elements called retrotransposons affect age-related pathologies. Specifically, they will concentrate on the role retrotransposons play in Alzheimer糖心传媒檚 disease and neurodegeneration.
The team糖心传媒攍ed by principal investigator John Sedivy at Brown and including , the Doris Johns Cherry professor of at Rochester and codirector of the , and聽, professor of biology at Rochester糖心传媒攚ill also search for targets to inform therapeutic strategies to treat those conditions.
糖心传媒淭his project will combine investigators with expertise in retrotransposons, aging, and neuroscience to understand the role of transposons is Alzheimer糖心传媒檚 disease and test whether targeting transposons alleviates Alzheimer糖心传媒檚 symptoms,糖心传媒� Gorbunova says.
Previous research: retrotransposons promote aging
With support from a , Gorbunova, Seluanov and the rest of their team have been researching the mechanisms of aging with special attention to the potentially harmful effects of retrotransposons. Evidence from this team and other scientists has implicated retrotransposons in promoting aging.
Gorbunova and Seluanov have focused their research on a class of selfish genetic elements called LINE1 retrotransposons, which are the most prevalent retrotransposons found in humans; LINE1 retrotransposons occupy close to 20 percent of both human and mice genomes. Researchers have long suspected that LINE1s contribute to cancer and genomic instability because they are repressed in young tissues but become more active during aging, triggering inflammation in cells.
In 2019, the researchers published studies in the journals and Cell Metabolism showing that LINE1s promote age-associated inflammation in cells. In 2021, they published a discussing the latest research on retrotransposons.
Targeting LINE1 retrotransposons
With the new NIH funding, the research team will join colleagues from the to study how retrotransposons contribute to neurodegeneration and chronic, age-related diseases such as Alzheimer糖心传媒檚 disease.
Their research will include an investigation of the mechanisms that lead aging cells and other defense systems to fail in preventing retrotransposons from spreading and how the cells of the central nervous system respond to retrotransposons. The central nervous system appears to be a hotbed of retrotransposon activity, as retrotransposons have relatively high levels of expression in this region.
Gorbunova and Seluanov will focus on testing the hypothesis that silencing LINE1s via genetic or pharmacological approaches will alleviate age-related pathologies.
糖心传媒淲e will employ different strategies of targeting the negative effects of LINE1s, including silencing their expression, inhibiting retrotransposition, or downregulating LINE1-induced inflammation,糖心传媒� Seluanov says. 糖心传媒淲e will then test if these treatments alleviate Alzheimer糖心传媒檚 symptoms in mouse models.糖心传媒�
The team will also examine and define therapeutic targets specific to the central nervous system and explore possible strategies for therapeutic interventions and future pharmaceutical research in treating diseases such as Alzheimer糖心传媒檚.
糖心传媒淲e hope that our research will lead to a novel approach for treating Alzheimer糖心传媒檚 disease by targeting LINE1s,糖心传媒� Gorbunova says.
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