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The identification of dopaminergic neurons using Tyrosine Hydroxylase in Parkinson's research and LRRK2

Thu, 08/25/2016 - 08:49

Tyrosine hydroxylase (TH) is a crucial enzyme involved in the biosynthesis of dopamine, norepinephrine and epinephrine in the brain.  Specifically, TH catalyzes the conversion of l-tyrosine to l-dihydroxyphenylalanine (l-dopa).  The importance of tyrosine hydroxylase was established early on in when Zhou et al found that TH deficient mice had a lethal phenotype.  While TH is vital to neurotransmitter and neural hormone development, mutations in TH are not solely responsible for Parkinson’s disease (PD).  In fact, mutations in the LRRK2 gene and marked loss of dopaminergic neurons in the substantia nigra are the hallmark signs of PD. However, mutations in TH lead to dystonia DOPA-responsive autosomal recessive disorder, also known as autosomal recessive Segawa syndrome. Using a TH antibody in Parkinson’s research is an effective and popular way to monitor dopaminergic neuron viability. 

TH antibody

Tyrosine Hydroxylase Antibody [NB300-109] - Dopamine neurons in the mouse substantia nigra. Image from confirmed customer review.

The first application of a TH antibody is by Tsika et al and was used to further understand the pathology of LRRK2 mutations in familial autosomal dominant PD.  While LRRK2 mutations lead to dopaminergic neurodegeneration in most cases, there are many transgenic mouse models where other hallmark signs of PD have occurred without direct dopaminergic loss.  With this information, Tsika et al designed a R1141C LRRK2 transgenic mouse model where R1141C LRRK2 was dominantly expressed in dopaminergic neurons.  Using a TH antibody in immunohistochemistry, alongside unbiased stereological methodology, Tsika et al did not find any significant data regarding R1141C LRRK2 and dopaminergic neuron degeneration.  While dopamine structure appeared the same in the mutant vs. control mouse, it was determined that expression of LRRK2 was not sufficient enough to draw large conclusions.  However, after further neuropathological studies and testing, there was a correlation between R1141C LRRK2 and neuron structure in aging mice. 

The next application of a TH antibody in PD research is in a Drosophila melanogaster model from Venderova et al.  Venderova et al used a TH antibody to investigate the potential interactions between LRRK2 and Parkin, DJ-1 and PINK-1 in Drosophila after finding interesting phenotypes of the LRRK2 mutation in flies. Similar to Tsika et al, this group developed Drosophila lines carrying either mutant or WT LRRK2.  Through immunohistochemistry of the dorsolateral posterior protocerebral (PPL1), lateral posterior protocerebral (PPL2) and two dorsomedial posterior protocerebral clusters (PPM1/2 and PPM3) sections of 50-day-old flies, they found that introduction of the LRRK2 mutation in aging flies did in fact result in dopamine neurodegeneration.  LRRK2 was also specifically mutated in the eye and found to have severe phenotypes leading to the investigation of potential interaction with other notable recessive PD genes. 

Novus Biologicals offers Tyrosine hydroxylase reagents for your research needs including:

PMID: 25174890
PMID: 19692353
PMID: 10560033

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