Application
Improved study of neurodegenerative diseases on mice.
Key Benefits
- Ability to study neuromelanin’s association with neurodegenerative diseases with mice.
- Researchers can analyze overexpression of tyrosinase on specific cell types.
Market Summary
Neurodegenerative diseases such as Alzheimer’s and Parkinson’s are the most common diseases and affect millions worldwide with limited treatment options. Neuromelanin (NM) in the pre-synaptic terminal of dopamine neurons is emerging as a primary player in the etiology of neurodegenerative disorders, including Parkinson’s disease. It is a dark brown intracellular pigment that accumulates within the brains of those with neurological conditions and may be a marker for the disease. Unfortunately, animals that are used in the study of these conditions lack NM, which is a challenge for researchers and pharmaceutical companies. Hence, developing animal models of neurological disorders that express NM may help develop new medicines and diagnostics for these devastating diseases.
Technical Summary
Previously, Carballo-Carbajal et al (2019) generated a novel adeno-associated virus (AAV) vector which overexpresses human tyrosinase (hTyr), which is responsible for melanin production in the skin and hair, using a ubiquitous promoter that can drive expression in all types of neurons. Here, Emory researchers improved on that design by generating a hTyr AAV vector that is Cre-dependent and therefore can only be expressed at the presence of bacterial enzyme Cre recombinase (a type of tyrosine enzyme derived from P1 bacteriophage). AAV5-DIO-hTyr can therefore provide the human-like catecholamine cell-type specificity when infused into a tyrosine hydroxylase-Cre transgenic mouse or noradrenergic cell-type specificity when infused into a dopamine -hydroxylase-Cre transgenic mouse. The viral vector-mediated hTyr expression can be visualized by the naked eye or by light microscopy by the neuromelanin-like (darkened) pigmentation produced in mouse catecholamine neurons.
Developmental Stage
Animal testing conducted.
Publication: Carballo-Carbajal, I., Laguna, A., Romero-Giménez, J. et al. (2019) Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis. Nat Commun 10, 973. https://doi.org/10.1038/s41467-019-08858-y