Amyloid protein clusters in neurons are involved in neurodegenerative diseases such as Parkinson’s or Alzheimer’s.
Parkinson’s disease, Alzheimer’s disease, cerebral degeneration, amyotrophic lateral sclerosis, all these neurodegenerative diseases have one thing in common: the death of neurons associated with the accumulation of so-called amyloid proteins (different depending on the disease).
Abnormal proteins aggregate in sorts of “balls of wool” which fill the neurons then are transmitted from neurons to neurons, between the different cerebral regions leading to inflammation (a reaction of the immune defense system) and cell death. The central question was therefore to know where these amyloid proteins came from.
Researcher Shu Chen, from Case Western Reserve University in Cleveland, and his colleagues have shown that they come from our intestines, and more specifically from bacteria in the intestinal flora. Until now, we did not know how the first abnormal proteins appear, which fold badly and accumulate in neurons.
A significant inflammatory reaction was also observed around the brain regions where these proteins aggregate, without it being known whether or not it causes the death of neurons. On the other hand, it was known that amyloid proteins are already present in the intestines and intestinal neurons of patients sometimes 20 years before Parkinson’s disease is diagnosed.
It’s all in the gut
Our intestines contain more than 1.5 kilograms of bacteria. This intestinal flora or microbiota has many roles in digestion, against inflammation, etc. These bacteria are mostly not only harmless, but also essential to our survival. In 2002, it was discovered that some of them produced amyloid proteins, useful for their proliferation, adhesion and resistance.
The most studied are the “curli” proteins, secreted by Escherichia coli bacteria. Chen and his colleagues speculated that these gut flora amyloid proteins cause other amyloid proteins to appear in brain neurons.
They chose to study the aggregation of one of these proteins, alpha-synuclein, which accumulates in the neurons of patients suffering from Parkinson’s disease. To do this, they fed 344 aged rats and C. elegans worms (genetically modified to express human alpha-synuclein) with curli-producing Escherichia coli bacteria for two or three months, with other animals receiving modified bacteria. to no longer produce curli.
Result: the rats having received the E. coli secreting the curli showed aggregated alpha-synuclein proteins in the intestine and in the intestinal neurons, but also in the neurons of the brain. The worms developed clusters of alpha-synuclein proteins in their muscle cells.
Conversely, animals exposed to non-curli-producing bacteria developed very few amyloid aggregates. In addition, the appearance of amyloid proteins provoked an intense local inflammatory reaction in the rat brain, comparable to that observed in the brain of patients suffering from neurodegenerative diseases.
Intestinal flora in poor health: worsened inflammation
How do amyloid proteins secreted by bacteria indirectly affect neurons? Scientists put forward three hypotheses. The presence of bacterial aggregate proteins could cause an overexpression of alpha-synuclein throughout the organism, which would then promote its aggregation.
Unless the aggregation is transmitted, almost step by step, to other proteins. Or that the immune activation generated in the intestines by bacterial amyloid proteins leads to an immune reaction and inflammation in the brain; inflammation which would then be the cause of cerebral protein aggregation.
This study is one of the first to demonstrate that the microbiota is capable of causing the aggregation of abnormal proteins in brain neurons. This is a new avenue of research to better understand neurodegenerative diseases, or even treat them, given that we now have many tools to study and act on the intestinal flora.
The health of the intestines and the intestinal flora through diet and the regular intake of probiotics remains a priority for those who care about their present and future health.
Chen et al., Exposure to the functional bacterial amyloid protein curli enhances alpha-synuclein aggregation in aged fischer 344 rats and Caenorhabditis elegans, Nature
See also: Vision problems: perhaps the first signs of Alzheimer’s