Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus.

ABSTRACT: The locus coeruleus (LC), the major source of norepinephrine (NE) in the brain, is among the earliest site of pathology in both Alzheimer's disease (AD) and Parkinson's disease (PD), and it undergoes catastrophic degeneration later in both disorders. Dysregulation of the LC is thought to contribute to prodromal symptoms of AD and PD such as anxiety and sleep disturbances, while frank LC loss promotes cognitive decline. However, the mechanisms responsible for its selective vulnerability are unknown. It has been suggested that neuromelanin (NM) pigment contributes to LC susceptibility, but causal relationships have been difficult to test because rodents do not naturally produce NM. Here, we report that viral-mediated expression of human tyrosinase induced pigmentation in mouse LC neurons tha

SUBMITTER: Iannitelli AF 

PROVIDER: S-EPMC10028911 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature