Parkinsons

By Michalina Hanzel, PhD

By Michalina Hanzel, PhD

By Christina Towers, PhD.

Tyrosine hydroxylase (TH) is a crucial enzyme involved in the biosynthesis of dopamine, norepinephrine and epinephrine in the brain.

DOPA decarboxylase (DDC) is responsible for catalyzing the conversion of aromatic amino acids into their corresponding amines during the synthesis of several important neurotransmitters. Specifically, DDC catalyzes the decarboxylation of L-DOPA to dopamine, L5-HTP to serotonin, L-histidine to histamine, phenylalanine to phenethylamine, L-tyrosine to tyramine, and tryptophan to tryptamine.

Parkin/PARK2 is a cytosolic enzyme which gets recruited to cellular mitochondria damaged through depolarization, ROS or unfolded proteins accumulation, and exert protective effects by inducing mitophagy (mitochondrial autophagy). Parkin induces mitophagy by promoting mitofission (mitochondrial division) and by ubiquitinating mitochondrial proteins to facilitate their recognition/recruitment to the autophagosomal surface.

PTEN-induced putative kinase 1 (PINK1) is a serine/threonine kinase with important functions in mitochondrial quality control. Together with the Parkin protein, PINK1 is able to regulate the selective degradation of damaged mitochondria through autophagy. Normally PINK1 is imported into the mitochondria where it is targeted for proteolytic cleavage. This cleavage event results in unstable products and is the reason PINK1 is difficult to detect in healthy mitochondria.

The protein PINK1 is a mitochondrial-located serine/threonine kinase (PTK) that maintains organelle function and integrity. It not only protects organelles from cellular stress, but it also uses the selective auto-phagocytosis process for cleaning and clearing cell damage. Exner et al initially reported that, in humans, a PINK1 deficiency is linked to autosomal recessive incidences of both neurodegenerative pathology and Parkinson's Disease (PD) (1).

PINK1 (PTEN induced putative kinase 1) is a mitochondrial serine/threonine kinase which maintains mitochondrial function/integrity, provides protection against mitochondrial dysfunction during cellular stress, potentially by phosphorylating mitochondrial proteins, and is involved in the clearance of damaged mitochondria via selective autophagy (mitophagy).

In the synthesis pathway for the catecholamines - dopamine, epinephrine, and norepinephrine, tyrosine hydroxylase is the rate-limiting enzyme. Through alternative mRNA splicing, a wide molecular diversity of TH isoforms are generated that are tissue-specific and carry varied enzymatic activities, allowing for differential neurotransmitter availability at various synapses.