Please Tell Me About the Causes of Multiple System Atrophy.

After visiting many hospitals, I was finally diagnosed with Multiple System Atrophy. Being told I had a rare disease suddenly left me feeling completely lost. What causes Multiple System Atrophy?

S.K., Tokyo

Multiple System Atrophy is caused by the degeneration of a protein called α-synuclein, which regulates nerve transmission in the brain.

α-synuclein is a protein that regulates the transmission of brain signals responsible for motor balance and emotional expression. When α-synuclein degenerates and clumps together, it progressively impairs the ability to move and express emotions.

Additionally, research has identified seeds in the blood serum of patients that can induce Multiple System Atrophy, and these seeds have been successfully extracted (published in *Nature Medicine*). Recently, Multiple System Atrophy has been considered a prion-like disease that may spread and propagate.

The causes are gradually being uncovered.
In the near future, a drug to cure Multiple System Atrophy at its root may be developed.

Acupuncturist Hiroaki Yoshiike

People Prone to Multiple System Atrophy

It is believed that certain genetic predispositions may increase susceptibility to Multiple System Atrophy.

Having relatives with Parkinson’s disease or Dementia with Lewy Bodies appears to raise the likelihood of developing Multiple System Atrophy. It is thought that individuals with a genetic predisposition for the disease may develop it due to external factors such as lifestyle, stress, or environmental influences.

What Is α-Synuclein?

α-synuclein is an essential protein involved in synaptic communication in neurons.

α-synuclein is believed to regulate synaptic function in the dopamine pathways, which are responsible for fine motor adjustments and emotional regulation. When the function of dopamine pathways declines, it gradually affects motor coordination, cognitive functions, emotions, and learning.

Until recently, α-synuclein could not be visualized in living organisms. However, according to an August 2022 announcement by the National Institutes for Quantum Science and Technology, α-synuclein was successfully imaged using a positron emission tomography (PET) scanner. This breakthrough is expected to lead to advancements in diagnostic technologies and the development of fundamental treatments for Multiple System Atrophy.

Causes of α-Synuclein Misfolding

α-synuclein misfolds due to seeds.

In May 2023, it was announced that α-synuclein seeds, which cause the misfolding of α-synuclein, were discovered. Multiple types of seeds exist, and the location of α-synuclein accumulation varies depending on the seed, leading to Parkinson's disease, Dementia with Lewy Bodies, or Multiple System Atrophy.

α-synuclein is originally a water-soluble protein, but it becomes insoluble when misfolded, accumulating as inclusions in glial cells that support brain neurons. This accumulation eventually becomes toxic, causing rapid atrophy of brain neurons.

How Seeds Invade Healthy Brain Neurons

The misfolding of α-synuclein caused by seeds has been found to involve prion-like cellular infection.

It was discovered that injecting α-synuclein seeds from Multiple System Atrophy into the brains of healthy mice causes their brain neurons to transform into MSA-like neurons over approximately one year. This finding has sparked discussions that MSA involves prion-like infections caused by abnormal proteins.

Prion infections differ entirely from bacterial or viral infections; they occur when abnormal proteins spread through contact with healthy tissues. Abnormal seeds, primarily composed of misfolded α-synuclein, are taken up by neurons, causing cellular degeneration and propagation between cells.

Currently, the development of new drugs targeting these seeds is underway, along with clinical and experimental trials.