Background pattern of a brain with neural connections

Team Mobley

Reconstructing the Lost Nigrostriatal Circuitry in Parkinson’s Disease

2021-Present

This project aims to understand the latent neurogenic program in astrocytes and leverage this program to make new neurons to reconstitute the lost neural circuitry to degeneration. We will determine how astrocytes are progressively converted to neurons and demonstrate their functional integration into the existing neural networks in the brain. We will elucidate age-dependent barriers to cell fate reprogramming, explore the molecular basis for generating different subtypes of neurons in different brain regions, and determine the functional interplay between reactive gliosis and neuronal reprogramming. These studies will enable the development of a novel cell replacement therapy to reverse Parkinson’s disease.

Tags
Neural circuitry

Leadership

William (Bill) Mobley

William (Bill) Mobley

Lead PI (Core Leadership)

Steve Dowdy

Steve Dowdy

Co-PI (Core Leadership)

Xiang-Dong Fu

Xiang-Dong Fu

Co-PI (Core Leadership)

Allen Wang

Allen Wang

Co-PI (Core Leadership)

Yuanchao Xue

Yuanchao Xue

Co-PI (Core Leadership)

Peter Shaw

Peter Shaw

Project Manager

Project Highlights

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Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain

Cell replacement therapy represents a promising approach for treating neurodegenerative diseases. Contrary to the common addition strategy to generate new neurons from glia by overexpressing a lineage-specific transcription factor(s), a recent study introduced a subtraction strategy by depleting a single RNA-binding protein, Ptbp1, to convert astroglia to neurons not only in vitro but also in the brain. Given its simplicity,...

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