Rapid-Eye-Movement Sleep Defects: Mechanism & Target in Neurodegeneration

Faculty: Chinnakaruppan Adaikkan (CBR) & Arnab Barik (CNS)

We know that there is no cure for neurodegenerative diseases yet.

Rapid-eye-movement (REM) sleep behavior disorder (RBD) represents an early manifestation and a prodromal phenotype of neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and Alzheimer’s disease (AD).

Since the phenoconversion rate from RBD to PD or AD is quite compelling, the period between RBD and neurodegeneration offers a critical time window to delay the onset and progression of PD and AD.

In this project, combining established and novel mouse models with in vivo neurophysiology, biochemistry, behavior, and closed-loop brain stimulation, we will decipher a) how pS129, a pathogenic form of phosphorylated alpha-synuclein, contributes to RBD and b) test the hypothesis that regulating the cortical oscillations during REM in the initial stages of RBD would delay the onset of neurodegeneration and improve dementia in mouse models of PD and AD.

Further reading:

1. https://doi.org/10.1038/s41572-018-0016-5
2. https://doi.org/10.1016/j.tins.2019.11.001
3. https://doi.org/10.1523/jneurosci.1828-22.2023
4. https://doi.org/10.1016/s1353-8020(13)00400-8
5. https://doi.org/10.1093/brain/awaf003
6. https://doi.org/10.1016/j.parkreldis.2021.04.007
7. https://doi.org/10.3389/fneur.2020.547288