Function (biology)

Cell biology

Neuroscience

Disease

Pathogenesis

Biology

Internal medicine

Immunology

Medicine

Cognition

Computational biology

Cancer research

Aging Cell

The orphan nuclear receptor Nurr1 (also known as NR4A2 ) is critical for the development and maintenance of midbrain dopaminergic neurons, and is associated with Parkinson's disease. However, an association between Nurr1 and Alzheimer's disease (AD)‐related pathology has not previously been reported. Here, we provide evidence that Nurr1 is expressed in a neuron‐specific manner in AD‐related brain regions; specifically, it is selectively expressed in glutamatergic neurons in the subiculum and the cortex of both normal and AD brains. Based on Nurr1’s expression patterns, we investigated potential functional roles of Nurr1 in AD pathology. Nurr1 expression was examined in the hippocampus and cortex of AD mouse model and postmortem human AD subjects. In addition, we performed both gain‐of‐function and loss‐of‐function studies of Nurr1 and its pharmacological activation in 5XFAD mice. We found that knockdown of Nurr1 significantly aggravated AD pathology while its overexpression alleviated it, including effects on...

Nurr1 (NR4A2) regulates Alzheimer’s disease‐related pathogenesis and cognitive function in the 5XFAD mouse model