Parkinson’s disease – causes, symptoms, diagnosis, treatment & pathology

Parkinson’s disease, which
is sometimes called Parkinson disease, Parkinson’s, or PD, is a movement disorder where the dopamine-producing
neurons in the substantia nigra of the brain undergo degeneration. Parkinson’s is one of the most common neurological
disorders. It’s a progressive, adult-onset disease,
and it gets more common with age. Most of the time, there’s no known cause. But in a few cases, there might be a genetic
cause, like mutations in the PINK1, parkin, or alpha synuclein genes, and in rare cases,
Parkinsonian symptoms may be caused by MPTP, a toxic impurity that can be found in the
recreational drug MPPP or desmethylprodine, which is a synthetic opioid. In other people, one or more risk factors,
rather than a single outright cause, might contribute to Parkinson’s, for example pesticide
exposure or DNA variants in genes like LRRK2. No matter the cause is, Parkinson’s derives
from the death of dopamine-producing, or dopaminergic, neurons in the substantia nigra. The name substantia nigra means “black substance,”
since it is darker than other brain regions when you look at a slice of the brain on an
autopsy. We usually refer to the substantia nigra as
if it’s in a single location, but there are actually two of these regions in the brain,
one on each side of the midbrain. The substantia nigra is a part of the basal
ganglia, a collection of brain regions that control movement through their connections
with the motor cortex. In Parkinson’s, these darkened areas of
substantia nigra gradually disappear. Under a microscope, Lewy bodies, which are
eosinophilic, round inclusions made of alpha-synuclein protein are present in the affected substantia
nigra neurons before they die. The function of alpha-synuclein is unknown,
as well as the significance of Lewy bodies, and they are both found in other diseases
like Lewy body dementia and multiple system atrophy. The substantia nigra actually can be split
into two sub-regions. First, there’s the pars reticulata, which
receives signals from another part of the basal ganglia called the striatum, which is
a term for the caudate and putamen put together, and relays messages to the thalamus via neurons
rich in the neurotransmitter GABA, also known as gamma-aminobutyric acid. Second, there’s the pars compacta, and this
is the part of the substantia nigra affected in Parkinson’s. The pars compacta sends messages to the striatum
via neurons rich in the neurotransmitter dopamine, forming the nigrostriatal pathway, which helps
to stimulate the cerebral cortex and initiate movement. Therefore, when substantia nigra pars compacta
neurons die, the individual may be in a hypokinetic or low movement state which is commonly seen
in Parkinson’s. In addition to simply initiating movements,
the substantia nigra helps to calibrate and fine tune the way that movements happen, which
leads to the clinical features of Parkinson’s. First there’s tremor, which is an involuntary
shakiness most noticeable in the hands—characteristically called a “pill-rolling” tremor because
it looks like someone rolling a pill between their thumb and index finger. This is a “resting tremor,” meaning it
is present at rest and diminishes with intentional movement. Next there’s rigidity, which refers to stiffness
that can appear as “cogwheel” rigidity, which is when there are a series of catches
or stalls as a person’s arms or legs are passively moved by someone else. Rigidity is also responsible for the stooped
posture and an almost expressionless face that some individuals with Parkinson’s might
have. Next up is Bradykinesia is slow movement,
hypokinesia is lessened movement, and akinesia is an absence of movement, and all three result
from difficulty initiating movements. Examples of this are having the legs freeze
up when trying to walk and also walking with a shuffling gait, or small steps. Finally, a late feature of the disease is
postural instability which causes problems with balance and can lead to falls. Despite these multiple effects on movement,
Parkinson’s Disease does not produce weakness. This helps differentiate it from diseases
that affect the motor cortex or corticospinal pathway. In addition, the resting tremor of Parkinson’s
Disease helps to differentiate it from cerebellar diseases, which might result in an action
or intention tremor, which is a tremor that’s essentially the opposite of a resting tremor,
where the tremor actually gets worse with movement. Also, both bradykinesia and postural instability
help differentiate Parkinson’s from essential tremor. Of which an action tremor is also a hallmark
feature. Non-motor brain functions can be affected
in Parkinson’s as well, leading to additional common symptoms including depression, dementia,
sleep disturbances, and difficulty smelling. These are thought to come about because of
dysfunction in dopaminergic signalling in other parts of the brain beyond the substantia
nigra, for example in the prefrontal cortex leading to cognitive symptoms, and also possibly
from issues with other neurotransmitters like acetylcholine. Fortunately, there are treatments that help
with Parkinson’s symptoms, although none stop the progressive neurodegeneration. The main strategy here is to increase the
amount of dopamine signalling in the brain. Dopamine itself can’t cross the blood-brain
barrier, but its precursor levodopa can, and once in the brain, levodopa is converted to
dopamine by dopa decarboxylase, most importantly within the remaining nigrostriatal neurons. Peripheral dopa decarboxylase also exists,
which can metabolize levodopa into dopamine before it gets through the blood brain barrier,
and—via additional enzymes—metabolize it into other catecholamines like epinephrine,
which can cause unwanted side effects like arrhythmias. This is exactly why levodopa is administered
with carbidopa, a dopa decarboxylase inhibitor that isn’t able to cross the blood-brain
barrier. Another strategy is using amantadine, which
is also an antiviral medication that increases endogenous dopamine production, although the
mechanism here is still being worked out. A different strategy is to use dopamine agonists
that can stimulate dopamine receptors and basically trick the brain into thinking there’s
more dopamine than there really is, like bromocriptine, which is an ergot or fungal derivative, as
well as pramipexole and ropinirole, which are not ergot derivatives. Alright the next dopamine-directed class of
therapies are inhibitors of COMT, catecholamine-O-methyltransferase, which is an enzyme that degrades dopamine
and levodopa. COMT inhibitors like entacapone and tolcapone
are only given with levodopa to prevent the enzyme from breaking it down outside the central
nervous system, thus allowing more of it to enter the brain. . Very similarly, there are medications like
selegiline which inhibits monoamine oxidase B, also known as MAO-B, which is another enzyme
that metabolizes dopamine. Since usually there’s this balance of signaling
between dopamine and acetylcholine, a loss of dopamine reaching the striatum increases
the relative amount of acetylcholine signalling there. Therefore anticholinergics can be given to
restore the balance of cholinergic and dopaminergic signaling, like benztropine, which improves
the tremor of PD. A special treatment available to help treat
PD is deep-brain stimulation. Which involves an implantable device that
directly sends electrical signals to the basal ganglia which counteracts the aberrant signaling
in Parkinson’s. The term “parkinsonism” is sometimes used
to describe symptoms of Parkinson’s that are seen in other nervous system diseases
like Lewy body dementia, Wilson disease, and Pick disease, as well as side effects of a
medication, like antipsychotics such as haloperidol, which blocks dopamine receptors, and metoclopramide,
a dopamine antagonist sometimes used to treat vomiting. Alright, as a quick recap—Parkinson’s
is a progressive movement disorder caused by degeneration of dopamine-producing neurons
in the substantia nigra, specifically in the pars compacta, which leads to resting tremor,
rigidity, problems initiating movement, and postural instability, and for which therapy
primarily focuses on increasing brain dopamine.


  1. That moment when you already watched the older video and notice the differences.😅 Thank you Osmosis for the updates and the upgrowing quality 💕

  2. In February last year, out of nowhere, my eyes became light sensitive, had slurred speech, my vocal cords seemed strained and my legs/hands began to shake uncontrollably, and I was diagnosed of PARKINSON DISEASE. I started out taking only Azilect, then Mirapex and sinemet as the disease progressed but didn’t help much. In September, I started on PARKINSON DISEASE TREATMENT PROTOCOL from Herbal Health Point (ww w. herbalhealthpoint. c om). One month into the treatment, I made a significant recovery. After I completed the recommended treatment plan, almost all my symptoms were gone. Its been 6 months since I completed the treatment, I live a better life

  3. After my PD diagnosis, I started out taking only Azilect, then Mirapex and sinemet as the disease progressed but didn’t help much. In July last year, I started on PARKINSON DISEASE TREATMENT PROTOCOL from Herbal Health Point (ww w. herbalhealthpoint. c om). Few months into the treatment, I made a significant recovery. After I completed the recommended treatment plan, almost all my symptoms were gone, had wonderful improvement with my movement and tremors . Its been 6 months since I completed the treatment, I live a better life

  4. Just wondering if anyone knows anybody that has this disorder and tried psilocybin mushrooms (magic mushrooms), (Amsterdam truffles)? I hear it produces new neurological pathways.

  5. Many have found massive benefit from taking certain supplements, such as high doses of Vitamin B1 (thiamine), Mannitol and celery seed extract. Go to healthunlocked -> Parkinson's movement for the best forum IMO

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