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Why is the secret killer of Parkinson’s disease actually protein accumulation in the brain?
When exploring the pathophysiology of Parkinson's disease, scientists discovered that the key factor leading to the death of dopamine neurons is closely related to the aggregation of proteins in the brain. After these neurons begin to die, patients suffer impaired movement and develop symptoms such as tremors and rigidity, but the mechanisms behind all this remain puzzling to many experts.
Effects of protein aggregationProtein aggregation, particularly of alpha-synuclein, to form Lewy bodies is widely considered the pathological hallmark of Parkinson's disease.
Lewy bodies first appear in the olfactory bulb, medulla oblongata, and pons, and at this stage, the patient's symptoms are not obvious. As the disease progresses, Lewy bodies spread further to the substantia nigra of the midbrain, basal forebrain, and neocortex.
Although Lewy bodies have traditionally been considered the main cause of death, recent studies have shown that their presence may cause other harms and accelerate the death of neurons. Studies have shown that when alpha-synuclein exists in an aggregated state, it becomes toxic to cells and inhibits DNA repair function.
Autophagy disorders
Another important mechanism leading to neuronal death is the disruption of autophagy. Autophagy is the process by which internal cellular components are degraded and recycled. This mechanism is critical for maintaining brain health, and it is due to autophagy disorders that many Parkinson's disease patients experience cellular dysfunction.
In particular, abnormal autophagy may lead to mitochondrial damage, which further causes insufficient energy supply and ultimately causes neuronal death.
Changes in cellular metabolism
Mitochondria, the cells' energy source, also play a key role in Parkinson's disease. When mitochondria function abnormally, energy production is inhibited, which directly leads to cell death. Mutations in PINK1 and Parkin proteins affect the repair and degradation of damaged mitochondria.
The role of neuroinflammationWith age, DNA mutations accumulate in mitochondria, demonstrating increased susceptibility to neuronal death.
The process of neuroinflammation is also important in Parkinson's disease. Microglia, which serve as the brain's immune cells, become activated by nerve damage. When these microglia are in a pro-inflammatory state (M1), they secrete pro-inflammatory factors, which further lead to the death of motor neurons, forming a positive feedback loop.
Disruption of the blood-brain barrier
Finally, the destruction of the blood-brain barrier is also a factor that cannot be ignored. As the blood-brain barrier function is abnormal, it will lead to changes in the internal environment of the brain, further causing neuronal death. All of this is sometimes caused by pro-inflammatory factors or protein aggregation.
Impact on behaviorOnce the structure of the blood-brain barrier is damaged, neurons may face destructive effects and cause more health problems.
The importance of dopamine neurons in motor control cannot be underestimated. When a certain proportion of these neurons die, patients may experience a dopamine reduction of up to 80%, which directly affects the transmission of brain signals, causing tremors, Symptoms include stiffness and abnormal gait. All this makes patients' daily life increasingly difficult.
Despite continued investment in Parkinson's disease research, our understanding of these destructive mechanisms remains limited. Can we really find effective ways to fight these hidden killers?
