First of all I’d like to
dedicate this blog post to my late uncle who was a victim of Parkinson’s
disease. May he rest in peace…
Parkinson’s
disease was discovered by James Parkinson in 1867 and had initially called it
“Shaking palsey”. Parkinson’s is the 2nd most common
neurodegenerative disease after Alzheimer’s, and can be identified by shaking
hands (tremor), rigidity and posture instability; cased by the loss of neurons
in the Substantia Nigra (in the brain), and the lack of dopamine (dopamine
smoothes out skeletal muscle movements) due to the death of dopaminergic
neurones in the Substantia Nigra (black substance) in the brain and also the accumulation
of lewy bodies. Other symptoms of Parkinson’s are shuffling gait, depression
and anger.
It is prevalent in elderly people age 60-85 years. It is difficult to know if Parkinson’s is genetically caused but research goes into looking at relatives of Parkinson’s patients and the presence of lewy bodies in their brains. However there is still a very low amount of evidence for mutations of DNA and onset of Parkinson’s therefore research goes into genetics and environmental factors for the onset of this neurodegenerative disease.
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Currently
Parkinson’s is treated by the usage of dopamine (the neurotransmitter that isn’t
available in PD patients) along with the drug L-dopa as it cannot be
administered alone; Dopamine cannot cross the blood brain barrier without being
broken down by MaoB, (Monoamine Oxidase B) or COMT (Catechol-O-Methyl-Transferase).
New research = New Hope
And another treatment
for PD is the Prosavin injection. Prosavin is still in Phase I and II clinical
trials by Oxford Biomedica. Prosavin is a type of lentiviral gene-based therapy
that transfers genes coding for 3 enzymes (proteins) into the Substantia Nigra [3]:
- · Dopa decarboxylase
- · Tyrosine hydroxylase
- · GTP-cyclohydroxylase-1 (the enzyme involved in making monoamines like dopamine, serotonin and adrenaline)
This treatment
tries to restore and maintain the Dopamine levels in Parkinson’s patients and
it was found that patients reacted well to Prosavin and improved motor activity
in patients was found.
Other methods
of research go into enzymes and mutations in proteins that could be the
possible reason behind the onset of Parkinson’s disease, contrary to the
dopamine pathway.
Research
done by Toyoda et al suggested that the DJ-1/Park 7 gene is related to Parkinson’s
and can influence mitochondrial activity. The DJ-1 enzyme is known to help
prevent mitochondrial stress and this could mean there could be a mutation in
the DJ-1 gene that could possibly lead to Parkinson’s [1]
A single
cystiene mutation in the DJ-1 protein could decrease the body’s defences
against oxidative stress and increase copper cytotoxicity discovered last year
by a team led by Dr Odell et al. DJ-1
prevents oxidative stress by transporting a copper ion to the SOD1 metalloenzyme
that destroys free superoxide radicals in the body. However a single mutation
in the enzyme means that it will no longer be able to bind copper at the
cystiene residues and therefore will not be able to counteract oxidative
stress. [2]
The DJ-1
protein has been the centre of Parkinson’s disease research for a long time.
DJ-1 is predicted that it protects the mitochondria by maintaining the
electrochemical potential across the mitochondrial membrane; to maintain energy
manufacture.
Toyoda et al manipulated HeLA strains of human cells
to see the way they would react to the suppression of the DJ-1 protein, which
decreased the mitochondrial potential and administering the products of the
DJ-1 enzyme; glycolic acid and D-lactic acid, restored the membrane potential.
Further
research goes into whether the products of the DJ-1 enzyme can be administered
as a new therapeutic approach for Parkinson’s disease and finding a new
breakthrough discovery.
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[3] S.Palfi
, 2014 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61939-X/abstract
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