A team of researchers from the University of Castilla-La Mancha (UCLM) have located a potential therapeutic target against Alzheimer´s diesease in some proteins known as chaperones. They collaborate with a type of cells in the nervous system (astrocytes) to remove the pathological proteins which cause the apparation of clinical signs of the disease, such as memory deterioration.
The researcher from the University of Castilla-La Manch (UCLM) Melania González-Rodríguez is the main author of an article published in the International Journal of Molecular Sciences which located a new therapeutic target in a type of cells in the nervous system: the astrocytes. These remove the pathological proteins associated with clinical signs of Alzheimer´s disease such as cognitive deterioration, by means of another type of protein: chaperones. In the latter, which are in all cells, a new potential target could tackle a disease which affects over 800,000 people in Spain alone. Pathological proteins are removed by means of a process known as autophagy (by which the cells decompose) old, damaged and abnormal protein is destroyed.
The initial objective of the research by Melania González-Rodríguez, within the group Neuroplasticity and Neurodegeneration from the Ciudad Real Faculty of Medicine, entailed determining how neurons and other types of cells in the nervous system involved (the microglia and the astrocytes) affected an area of the brain, the hippocampus, in the case of Alzheimer´s. To do so, they compared brains with the disease and others without them and recorded the presence of different cells, measured the volume of the hippocampus and, in parallel to this, identified markers involved in the disease.
This approach responds to Alzheimer, characterised by the accumulation of two pathological proteins (β-amyloid peptide and tau). When clusters of these grow this causes the apparition of the clinical signs which are characteristic of the disease, such as deterioration of memory. At early stages of this disease these proteins accumulate in the hippocampus, an essential region for memory formation.
“The results indicated that not all subregions of the hippocampus are equally affected, but one in particular (CA1) with a lower volume, a loss of neurons and an increase in astrocytes. The proteomic results highlighted the possible role astrocytes had in removing pathological proteins by means of a process called autophagy mediated by chaperones”, the researcher González-Rodríguez explains.
This work covers the first study which uses stereology. That is, the three-dimensional interpretation of flat sections of materials or tissues to estimate the volume of different sub regions of the hippocampus as well as to analyse neurons and glia cells, using specific cell markers in samples with Alzheimer´s disease.
“The specific effect of one of the regions of the hippocampus, CA1, shows it is more vulnerable to the pathological changes produced in the illness and the participation of certain chaperones (BAG3 and HSP90AB1). On regulating levels of pathological proteins, they change them into interesting therapeutic targets for this illness”, the researcher states. She thanks the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and the Murcia biobanks (BIOBANC-MUR), of Tissues from the CIEN Foundation (BTCIEN) and the Principality of Asturias for their collaboration in this study.
The research has been funded by FEDER/UCLM, by the ministries of Economy and Competitivity and Science and Innovation; and the Castilla-La Mancha Regional Government.
UCLM Communication Office Ciudad Real, 17th of January 2022