Genetically encoded constitutive upregulation of β2 subunit containing neuronal nicotinic acetylcholine receptors is neuroprotective in female parkinsonian mice.

Parkinson's disease (PD) is expected to reach pandemic proportions by 2050, making the development of disease-modifying PD therapies an urgent and unmet medical need. Since nicotine and nicotinic ligands that are known to upregulate neuronal nicotinic acetylcholine receptors (nAChRs) can exert neuroprotection against clinical PD, this study sought to determine whether the upregulation of β2 subunit containing nAChRs (β2* nAChRs) alone is sufficient for neuroprotection. To this end, we developed a novel transgenic mouse model with ligand-independent β2* nAChR upregulation. Our findings suggest that inducing β2* nAChR upregulation alone may be a viable therapeutic strategy for PD. In addition, our new developed transgenic mice provide a valuable tool to study the role of nAChRs in other major neurological disorders.