Transcript Parkinson`s Disease

Parkinson’s Disease
Casey Wang
12301016032
History
• In 1817, James Parkinson published An Essay of the Shaking Palsy
• Novel described six patients as having “Involuntary tremulous
motion, with lessened muscular power, in parts not in action and
even when supported; with a propensity to bend the trunk forwards,
and to pass from a walking to a running pace: the senses and
intellect being uninjured.”
• Parkinson’s Disease was known as paralysis agitans (shaking palsy in
English), disease was later renamed by Jean-Marie Charcot
What is Parkinson’s Disease?
• A progressive neurodegenerative
disorder that affects movement
• Develops gradually, sometimes
beginning with a tremor in just one
hand. Stiffness, or slowing of
movement
• Parkinson's disease can't be cured,
medications may improve
symptoms. In later stages, surgery
to regulate certain regions of the
brain may be suggested
Who is affected?
• It is estimated that around 1 in 500 people are affected by Parkinson’s
disease and there are currently 127,000 people in the UK with the
condition.
• Average age for symptoms to start is around 60; (1 in 20 cases first
develop in people aged under 50)
• Men are one-and-half times more likely to get Parkinson’s disease
than women.
• Caucasians are at a higher risk. Rates are significantly lower in African
and Asian people.
Symptoms
• Tremor. Shaking usually begins in the limbs. One characteristic of
Parkinson's disease is tremor of your hand when it is relaxed (at rest).
• Slowed movement (bradykinesia). Occurs overtime, steps may
become shorter when you walk, or find it difficult to get out of a chair,
feet may stick to the floor as you try to walk, making it difficult to
move.
• Speech changes. Speech is soft, quick, slurred, and will hesitate
before talking. Monotone speech, without usual inflections
• Loss of automatic movements. Decreased ability to perform
unconscious movements, including blinking, smiling
• Rigid muscles
• Impaired posture and balance
• Writing changes
Causes
• Parkinson’s disease is caused by a loss of nerve cells in part of the
substantia nigra, which leads to a reduction in the amount of a
chemical called dopamine in the brain.
• Dopamine plays a vital role in regulating the movement of the body
and reduced dopamine level is responsible for many of the symptoms.
• The cause behind loss of nerve cells is unclear. Most experts think it is
due to a combination of genetic and environmental factors.
Changes in the Brain
• The presence of Lewy bodies.
Clumps of specific substances within
brain cells are microscopic markers
of PD. Researchers believe these
Lewy bodies hold an important clue
to the cause of Parkinson's disease.
• Alpha-synuclein is found within
Lewy bodies. An important natural
and widespread protein among
many. It's found in all Lewy bodies in
a clumped form that cells can't break
down.
Associated PD Genes
• Alpha-synuclein (SNCA) – located on chromosome 4 is a specific gene
that causes PD. Normally, the chromosome carries only a single copy
of the alpha-synuclein gene
– ‘Iowa kindred’ or ‘Spellman-Muenter kindred,’ carried 3 copies
of the gene.
• Other mutated genes known to cause PD: parkin, leucine-rich repeat
kinase 2, PTEN-induced putative kinase 1
• LRRK2 — encodes for the protein, Dardarin — is only associated with
PD. Mutations in the LRRK2 gene that lead to PD are most common in
people of North African, Basque, Portuguese
– Some with LRRK2 mutations develop PD in their 30s-40s, while
others develop the disease in their 80s, and others never
develop PD at all. People with LRRK2 gene mutations develop
dementia, while others develop a form of Parkinson’s that
shares features with amyotrophic lateral sclerosis (ALS)
Research
• Mitochondrial dysfunction induced by knockdown of mortalin is
rescued by Parkin
• Animal Models: neurotoxin 6-hydroxydopamine, also known as 6OHDA, creates a model of Parkinson’s disease in rats by targeting and
destroying dopaminergic neurons in the nigrostriatal pathway when
injected into the substantia nigra
• Neuroprotective treatments: A vaccine that primes the human
immune system to destroy alpha-synuclein, PD01A (developed by
Austrian company, Affiris), has entered clinical trials in humans
Treatment
Medications: alleviate symptoms by increasing brain’s supply of dopamine
• Carbidopa-levodopa (Parcopa). Levodopa, the most effective
medication, is a natural chemical that is converted into dopamine.
Levodopa is combined with carbidopa, which protects levodopa from
premature conversion to dopamine outside your brain, prevents
nausea.
– Side effects: hallucinations, swelling, sleepiness, hypersexuality,
gambling, and eating.
• MAO B inhibitors. Metabolizes brain dopamine. Prevents breakdown
dopamine by inhibiting the brain enzyme monoamine oxidase B
(MAO B).
• Catechol O-methyltransferase (COMT) inhibitors. mildly prolongs the
effect of levodopa therapy by blocking an enzyme that breaks down
levodopa
• Deep brain stimulation. Electrodes are connected to a generator
implanted in the chest that sends electrical pulses to the brain
Deep Brain Stimulation
1. A thin, insulated wire called a lead, or
electrode that is placed into the brain
2. The neurostimulator, similar to a
heart pacemaker, which is usually placed
under the skin near the collarbone, but
may be placed elsewhere in the body
3. Another thin, insulated wire called an
extension that connects the lead to the
neurostimulator
Because the cause of Parkinson's is unknown, definitive ways to prevent the disease
also remain a mystery. However, some research has shown that caffeine — which
is found in coffee, tea and cola — may reduce the risk of developing Parkinson's
disease. Green tea also may reduce the risk of developing Parkinson's disease.
Muhammad Ali – diagnosed in 1984.
(Head trauma, from activities such
as boxing)