Lewy bodies

Generality

Lewy bodies are small, round-shaped protein clusters that typically develop within the brain neurons of people with Parkinson's disease, Lewy body dementia, and multi-system atrophy.

The most important and abundant protein that makes up Lewy bodies is the so-called alpha-synuclein. The latter is a molecule of up to 140 amino acids, which appears to be involved in the release of important neurotransmitters, such as dopamine and acetylcholine.
Despite numerous studies conducted so far, and although there are no other abnormalities within diseased brain neurons (other than Lewy bodies), researchers have not yet established precisely how Lewy bodies are involved in the onset of Parkinson's. , Lewy body dementia and multi-system atrophy.

What are Lewy bodies?

Lewy bodies are small insoluble protein aggregates that form in the cytoplasm of brain nerve cells (i.e. neurons) of people with Parkinson's disease, Lewy body dementia (or Lewy body dementia), multi-system atrophy and some familiar forms of Alzheimer's disease.
The most important and most representative protein of Lewy bodies is the so-called alpha-synuclein. Sometimes other protein molecules are added to this, such as ubiquitin, alpha crystalline and the microtubule protein tau.
The only way to identify Lewy bodies is by analyzing brain tissue after death (examination post-mortem).

Neurological diseases characterized by the presence of Lewy bodies are also called synucleinopathies, with particular reference to alpha-synuclein.

WHAT IS ALPHA-SYNUCLEIN?

Alpha-synuclein is a protein of up to 140 amino acids, encoded by the SNCA gene and particularly abundant in the brain.
Although they have studied it for a long time, researchers have not yet definitively clarified its function.
According to the most accredited hypothesis, in brain neurons the alpha-synuclein would be localized at the level of the presynaptic terminations and, here, it would direct the vesicular transport of important substances called neurotransmitters.
Again according to what the scientific studies conducted in this regard, two of these neurotransmitters would be dopamine - which is a substance responsible for the fine control of voluntary and involuntary movements - and acetylcholine - which is involved in muscle contraction and more.
In the brain, alpha-synuclein can be found in neurons of the neocortex, hippocampus, substantia nigra, thalamus and cerebellum. Furthermore, it is also present in the glia cells, in the mammillary nuclei (the area between the diencephalon and the optic chiasm) and inside the mitochondria of some nerve cells (NB: mitochondria are cell organelles where ATP is produced) .
According to the latest findings, there are three isoforms of alpha-synuclein; they are distinguished by the number of amino acids: 140 for the most common isoform, 126 for alpha-synuclein-126 and 112 for alpha-synuclein-112.

LOCALIZATION OF LEWY'S BODIES AND TYPES

Lewy bodies are spherical masses found in two areas of the brain: in the brain stem and in the cerebral cortex.
Lewy bodies present in brain stem neurons are structures that, under the microscope, appear as dense, consistent structures surrounded by a very thin halo.
On the contrary, the Lewy bodies that are formed inside the nerve cells of the cerebral cortex are less defined aggregates than the previous ones and without any surrounding halo.

After the exams post-mortem of the brain tissues of patients with Parkinson's and Lewy body dementia, it was found that, while the Lewy bodies formed in the cells of the brainstem are characteristic of Parkinson's disease, those inside the neurons of the cerebral cortex are typical of Lewy body dementia.

ORIGIN OF THE NAME

Lewy bodies are so named because they were discovered in 1912 by a scientist named Frederic Lewy.
They were found during a study that F. Lewy was conducting on Parkinson's disease.

LEWY NEURITES

Sometimes alpha-synuclein can give rise to Lewy body-like structures called Lewy neurites.
Much less common and known than Lewy bodies, Lewy neurites contain granular material and alpha-synuclein filaments.
Just like Lewy bodies, they can be found, thanks to an appropriate examination post-mortem, in the neurons of people with Parkinson's disease, Lewy body dementia and multi-system atrophy.

In histological language, the term neuritis (in the masculine) indicates an extension of the neuron, such as an axon or a dendrite.
Therefore it should not be confused with neuritis (female) understood as an inflammatory process affecting the cranial or peripheral nerves.

Aftermath

The specific presence of Lewy bodies in the brain neurons of patients with synucleinopathies has led researchers to consider them the main culprits of these diseases.

However, research aimed at understanding the precise effects of these protein aggregates has not yet led to any certain results. In fact, there are currently only hypotheses.
Among the various theories proposed, the most accredited one argues that the presence of Lewy bodies interferes with the release of the neurotransmitters dopamine and acetylcholine by the presynaptic terminations.
Therefore, again according to the same hypothesis, due to the reduction of dopamine and acetylcholine levels, the interneuronal communication is compromised and the cells involved gradually face death.

Future prospects

The researchers are of the idea that, for the realization of an effective cure against synucleinopathies, it is absolutely necessary to clarify two aspects:

1. What is the mechanism that leads to the accumulation, in aggregates, of alpha-synuclein
2. The exact role played by Lewy bodies in the onset of the aforementioned pathologies.