Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across five fly Parkinsonism models.

ABSTRACT: The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson's dise

SUBMITTER: Pech U 

PROVIDER: S-EPMC11968104 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature