Parkinsons

Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis pathway of the catecholamines dopamine, epinephrine, and norepinephrine.

PINK1 is a protein serine/threonine kinase (PTK) that protects the organelles from cellular stress and controls selective autophagy to clear damage. Exner, et al. were among the first to report that PINK1 deficiency in humans was linked to autosomal recessive occurrences of Parkinson's disease (PD) and neurogenerative pathology (1).

The product of the Parkinson's disease 7 (Park7/DJ-1) gene belongs to the peptidase C56 family of proteins and appears to have two transcriptional variants. It is a positive regulator of androgen receptor-dependent transcription, and some evidence suggests it may also function as a redox-sensitive chaperone and sensor for oxidative stress. It apparently protects neurons against oxidative stress and cell death. Defects in the Park7 gene result in the autosomal recessive form of early-onset Parkinson’s disease.

Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone, or TQ) is derived from the seeds of the black cumin plant Nigella sativa. It has been reported to have a number of beneficial properties including anti-oxidative, anti-inflammatory and anti-tumorigenic activities and, like many other natural products, derivatives and analogues of thymoquinone are being synthesised in an effort to increase its therapeutic potential.

Parkinson's disease affects the nervous system which controls movement. Damage to the levels of dopamine in the brain impairs the ability to relay messages to parts of the body which control movement. While the exact cause of the disease is unknown, researchers are examining genetic causes linked to the LRRK2 gene and environmental factors.

Resources:

PINK1 is a protein serine/threonine kinase (PTK) that protects the organelles from cellular stress and controls selective autophagy to clear damage. Exner, et. al. were among the first to report that PINK1 deficiency in humans was linked to autosomal recessive occurrences of Parkinson's disease (PD) and neurogenerative pathology (1).

Alpha-synuclein is an abundant presynaptic protein expressed predominantly in brain, concentrated in presynaptic nerve terminals. Alpha-synuclein is deposited as fibrillary aggregates in neurons or glial cells which is a hallmark lesion in a subset of neurodegenerative disorders including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (all collectively referred to as synucleinopathies).

PINK1 (PTEN-induced putative kinase 1) is a mitochondrial directed serine-threonine kinase, that regulates normal mitochondrial function and transport vital to normal performance of neurons and neuronal survival. PINK1 has been shown to be localized to the cytosol, endoplasmic reticulum and the mitochondria. Some investigators have associated PINK1 localization to the intermembrane space, outer membrane insertion with a kinase domain facing towards the cytosol.

In the UK, 127,000 people are affected by the progressive neurodegenerative condition Parkinson's disease. Parkinson's is extremely difficult to diagnose in its early stages. The current method of diagnosis includes examination for physical signs of Parkinson's along with a detailed history of symptoms. The defining neuropathological characteristics of Parkinson's disease is Lewy bodies.

 Tyrosine hydroxylase catalyzes the rate-limiting step in the biosynthesis of the catecholamines dopamine, norepinephrine, and epinephrine. A hallmark of Parkinson's disease is the loss of dopaminergic neurons in the substantia nigra. Mutations in cases of autosomal recessive dopa-responsive dystonia and infantile Parkinsonism have also been identified recently.