Author: Jorge Moreno Charco
Prion diseases, or Transmissible Spongiform Encephalopathies (TSEs), could be defined as a group of neurodegenerative diseases related to the misfolding and spread of the endogenous prion protein through the central nervous system. This misfolded protein, in addition to spreading uncontrollably through the patient's brain, is highly neurotoxic, leading to neuronal death and, over time, the development of different symptoms in patients.
However, in the last decade the definition of prion diseases has expanded to include other much more common and well-known neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease, among others. These diseases fall into the group of diseases known as the prion-like (prion-like) diseases. They are so called because there is no direct link between these diseases and the prion protein responsible for TSEs, but they do have an aetiology very similar to TSEs, albeit with other endogenous proteins involved.
Several studies have demonstrated the clear relationship between the misfolding, aggregation and propagation of the Aβ and Tau proteins with Alzheimer's disease and of the α-synuclein protein with Parkinson's disease. It has been observed in different animal models how these proteins can malplex and spread in the brain and have been observed, in a malplexed state, in the brain of patients affected by these diseases. The relationship between the presence of these proteins and neuronal death is less clear, although various studies point in this direction.
However, more and more neurodegenerative diseases are joining the ranks of the diseases prion-like. A study published in June this year has shown how aggregates of the protein FUS (Fused in Sarcoma), a protein normally found in the nucleus where it performs its DNA repair function, caused the aggregation of the healthy FUS protein outside the cell nucleus in a propagation process very similar to that of the prion protein.
These aggregates have been linked to ALS before, but their direct relationship had not yet been demonstrated. In this work published by Dr. Vázquez-Sánchez et al. in vitro and then inoculated into an animal model expressing the human FUS protein have led not only to the presence of FUS aggregates in the brains of these animals, as occurs in ALS patients, but also accelerated the appearance of signs related to the disease. In other words, as with prion diseases, in ALS, the appearance of FUS aggregates and their spread through the central nervous system could be a key process in the development of the disease, and stopping this spread could be of enormous importance for future ALS therapy.
Taking all this information together, it is important to claim the importance of prion diseases within neurodegenerative diseases in general. Not only those previously mentioned, but also others such as frontotemporal dementia, dementia associated with Lewy bodies and other age-associated dementias are beginning to be included in recent years within the so-called prion-like. This is an important support for prion diseases, as research in this field is no longer only applicable to prion diseases, but much of this knowledge can be used to support the study of prion diseases. prion-likeThe same relationship occurs in the opposite direction, broadening the horizon of the study of neurodegenerative diseases as a set of closely related aetiological processes. The same relationship occurs in the opposite direction, broadening the horizon for the study of neurodegenerative diseases as a set of closely related aetiological processes.
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