Mechanisms of Parkinson’s disease
1.0 What is Parkinson’s Disease?
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease.
The core problem originates from the gradual loss of function in specific nerve cells located in a critical region of the brain. These neurons are responsible for producing and releasing dopamine, an essential chemical messenger. Dopamine plays a key role in transmitting signals that coordinate many fine movements and expressions—such as walking, speaking, writing, and even smiling.
As the disease progresses, the brain produces less and less dopamine. When dopamine levels become insufficient, the brain can no longer maintain proper motor control, and typical symptoms begin to appear.
Common Motor Symptoms
Slowness of movement (bradykinesia)
Speech difficulties
Muscle rigidity
Resting tremor
Balance problems and falls
Freezing of gait
Common Non-Motor Symptoms
(These may even appear before motor symptoms)
Depression and anxiety
Cognitive impairment and memory decline
Sleep disturbances and restless legs syndrome
Loss of smell
Bladder and gastrointestinal dysfunction
Fatigue and dizziness
Hallucinations and psychiatric symptoms
1.1 Mechanisms of Disease
Parkinson’s disease is primarily associated with the gradual death of dopamine-producing neurons in the substantia nigra, a key region involved in motor control. As these neurons die, the neural circuits responsible for movement begin to malfunction, resulting in the classic motor symptoms of the disease.
Current treatments mainly focus on replacing or mimicking dopamine (e.g., dopaminergic medications). However, their effectiveness decreases over time. Deep Brain Stimulation (DBS) is another treatment option.
Despite this, no existing therapy can slow or stop the progression of neurodegeneration.
The disease involves several interacting pathological mechanisms:
1.1.1 Protein Misfolding and Aggregation
The most characteristic feature is the misfolding and aggregation of alpha-synuclein, which forms abnormal structures known as Lewy bodies. These toxic protein accumulations damage neurons and may spread from cell to cell, accelerating disease progression.
Progression of Protein Aggregation
Alpha-synuclein
A normal protein found in neurons, likely involved in regulating neurotransmission.Protein Misfolding
In Parkinson’s disease, alpha-synuclein folds into an abnormal shape and begins to aggregate.Oligomers
Small, soluble clusters of misfolded alpha-synuclein.
These are considered the most toxic form, capable of severely impairing neuronal function.Fibrils
Oligomers further aggregate into insoluble long fibers.
These are more stable but less toxic.Lewy Bodies
Large, abnormal clumps consisting of alpha-synuclein fibrils and cellular debris.
These are a pathological hallmark found in the neurons of Parkinson’s patients.
Summary of the Relationship
Alpha-synuclein → Misfolding → Oligomers → Fibrils → Lewy bodies → Neuronal death (especially in the substantia nigra)
1.1.2 Mitochondrial Dysfunction
Mitochondria supply energy to cells and constantly adjust through fusion, fission, and transport to meet metabolic demands.
In Parkinson’s disease, these regulatory processes are impaired, leading to dysfunctional mitochondria that cannot support normal neuronal activity.
When mitochondria become old or damaged, they should be removed and replaced. However, in Parkinson’s disease, this renewal process is disrupted, causing the accumulation of defective mitochondria and accelerating neuronal injury.
Key Aspects of Mitochondrial Dysfunction
1. Reduced ATP Production
Mitochondria act as cellular “power plants.”
Damaged mitochondria cannot produce enough ATP, causing dopamine neurons—especially those in the substantia nigra—to gradually die.
2. Oxidative Stress
Dysfunctional mitochondria produce excessive reactive oxygen species (ROS), which damage proteins, lipids, and DNA, further accelerating neurodegeneration.
3. Abnormal Apoptosis
Mitochria regulate programmed cell death (apoptosis).
When dysfunctional, they may mistakenly trigger the death of healthy neurons, leading to premature loss of dopamine-producing cells.
4. Increased Alpha-synuclein Accumulation
Mitochondrial stress interferes with the removal of abnormal proteins.
This allows misfolded alpha-synuclein to accumulate and form Lewy bodies, further damaging neurons.
5. Mitochondria-related Genetic Mutations
Genes such as PINK1, SNCA, LRRK2, and Parkin regulate mitochondrial quality control.
Mutations lead to the buildup of defective mitochondria and contribute to neuronal death
1.1.3 Neuroinflammation
Microglia and astrocytes—immune cells of the central nervous system—normally help remove cellular debris.
However, during Parkinson’s disease, they may release excessive inflammatory substances that worsen neuronal damage.
Neuroinflammation in Parkinson’s disease is a chronic and persistent condition, occurring particularly in the substantia nigra.
Accumulated alpha-synuclein activates microglia, which release inflammatory cytokines such as TNF-α and IL-1β.
Instead of clearing abnormal proteins, these inflammatory chemicals damage nearby healthy neurons—especially dopamine-producing ones—leading to further degeneration and worsening of motor symptoms.
Recent research also shows that peripheral T-cells may cross the blood–brain barrier and enter the central nervous system, amplifying inflammation and neuronal injury.
This suggests that both the central and peripheral immune systems are involved.
Summary
Neuroinflammation is not only a consequence of the disease but likely one of the key drivers of neurodegeneration. Understanding this mechanism may help guide new anti-inflammatory treatments that could slow disease progression.
MATT for Parkinson’s Disease
MATT is a “three-in-one” neurological functional restoration system
MATT =
Microcurrent
Acupuncture
Thiamine (High-Dose B1)
Treatment
Meaning:
✔ Frequency-Specific Microcurrent (FSM)
Restores or modulates neural signaling
Reduces inflammation and repairs fascia and soft tissue
Regulates the brainstem, autonomic nervous system, and vagus nerve
Enhances neural activity and signal quality
Production of ATP
✔ Microcurrent Acupuncture
Faster and more stable than traditional acupuncture
Stimulates neural pathways with higher precision
Improves blood flow and local neural regulation
✔ High-Dose Thiamine (HDT)
Improves mitochondrial function
Enhances cellular energy metabolism (especially impaired in PD patients)
Supports dopaminergic neuronal function
Often produces immediate clinical improvements
What makes MATT unique?
MATT uses all three components simultaneously, not individually.
This combination is rarely done anywhere in the world, and produces the strongest clinical results.
Microcurrent Acupuncture (MA) & Parkinson’s Disease
Microcurrent acupuncture
How does microcurrent acupuncture work?
The endogenous electrical signals were discovered many years ago. Using modern techniques, the existence of these natural electrical fields has now been well established. These natural electrical signals play a pivotal role in many fundamental processes, one notably being in wound healing. By apply selected microcurrents which mimic these signals, healing can be enhanced for healing of brain cells.
Secondly, microcurrent stimulation is also known to provide a direct energy-related benefit to the mitochondria* within the cells, which are responsible for producing around 90% of cellular energy. The applied currents provide a means of an additional resource, which can be directly used in the production of ATP* (Adenosine Triphosphate). More ATP means faster cell repair and regeneration, which is why microcurrent therapy enhance recovering and reduce fatigue.
In its simplest form, microcurrent is able to facilitate naturally occurring electrical processes that are essential to the wellbeing of our nerve cells, by increasing blood flow blood circulation, which can help deliver oxygen and nutrients to the brain cells, potentially reducing inflammation and promoting healing. This means that regardless of the type damage or condition, virtually certain every Parkinson’s patient can gain notable benefits and improvements from using this technology, which is truly remarkable!
ATP* and Mitochondria*
ATP* (Adenosine Triphosphate) is the main energy source for cells, often called the "energy currency" of the body. It provides power for essential processes like muscle movement, nerve signaling, tissue repair, and metabolism.
Mitochondria* are like tiny power plants inside our cells. They make energy (called ATP) so the cells can work properly. Besides making energy, mitochondria also
1. Help control when a cell should die (apoptosis)
2. Store calcium
3. Support the immune system
4. Producing reactive oxygen species (ROS) that act like signals (but too much can be harmful)
They even have their own DNA, which shows they might have evolved from ancient bacteria.
ATP is primarily produced by the mitochondria, which generate energy by breaking down nutrients. More ATP means faster cell repair and regeneration, which is why microcurrent therapy help enhance healing and reduce fatigue.
Thiamine treatment (TT) & Parkinson’s Disease
Dr. Costantini and his colleagues (2015) suggested that the clinical improvements seen with high-dose thiamine occur because the surviving neurons in the substantia nigra can restore their energy metabolism when supplied with sufficiently high levels of vitamin B1.
Once cellular energy improves, several beneficial effects may follow:
increased synthesis and release of endogenous dopamine
enhanced activity of thiamine-dependent enzymes
better utilization of levodopa in patients who are taking it
Importantly, the patients did not have low blood levels of thiamine at baseline.
Despite this, high-dose B1 still produced significant symptom improvements.
This led Costantini to propose that Parkinson’s symptoms arise from a functional thiamine deficiency inside neurons, possibly due to:
dysfunction of the active intracellular transport of thiamine, or
structural abnormalities in thiamine-dependent enzymes