Tyrosine Hydroxylase Deficiencies and Neurodegeneration

Mon, 12/23/2013 - 15:51

Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis pathway of the catecholamines dopamine, epinephrine, and norepinephrine. Alternative mRNA splicing generates a wide molecular diversity of TH isoforms that are tissue specific and produce variations in enzymatic activity and neurotransmitter availability at various synapses. Parkinson's disease (PD) is due to a TH deficiency, as dopaminergic neuron degeneration and low dopamine levels are both consistently seen neurochemical abnormalities upon monitoring by tyrosine hydroxylase antibody staining (1).

Immunocytochemistry/Immunofluorescence: Tyrosine Hydroxylase Antibody Immunocytochemistry/Immunofluorescence: Tyrosine Hydroxylase Antibody

Tyrosine hydroxylase antibody staining in postmortem PD brain samples suggests that an N-terminus TH phosphorylation triggers its proteosomal degradation in a vicious cycle (2). The establishment of a useful transgenic knockout mouse model by Ramonet, el. al. depended on tyrosine hydroxylase antibody verification of clinical and neurochemical phenotype (2).  Some promising results obtained with tyrosine hydroxylase antibody were recently published in Cell identifying the parkin interacting substrate (ZNF746), which causes progressive classic PD dopamine neuron loss in a transcriptional coactivator PGC-dependent manner (3). Sekiguchi, et. al. used tyrosine hydroxylase antibodies to characterize the TH neuronal network of the frontal cortex and found that it is significantly altered in schizophrenia mouse models (4). Furthermore, dopamine studies in schizophrenia indicate that abnormal TH levels, as monitored by tyrosine hydroxylase antibodies, are intrinsic pathology characteristics but not functionally significant as they are treatment-unresponsive (5).

  1. PMID: 22483313
  2. PMID: 21494637
  3. PMID: 21376232
  4. PMID: 21458426
  5. PMID: 22509170

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