Alzheimer’s disease (AD) is the most common cause of dementia affecting more than 47 million people worldwide, being a major public health problem with a high economic impact. Due to the progressive increase in life expectancy, it has been proposed that its prevalence will triple in the next 30 years. AD is characterized by the accumulation of amyloid ß-peptide (Aß) which aggregates into ß-sheets forming neurotoxic oligomers and fibers. The fibers accumulate in the senile plaques of the cerebral parenchyma while the oligomers initiate the damage producing synaptotoxicity that will eventually produce neuronal death. Therefore the production and toxicity of Aß aggregates are determinants in the onset and progression of AD.
There are many experimental evidences that calcium dysregulation is related to the pathophysiology of the disease affecting to synaptic transmission, neuronal death and even increasing Aß production. Our group has recently screened 5,154 mutants of S. cerevisiae that overexpress Aβ, identifying a large number of genes involved in amyloid pathology. Of these we have selected 9 genes that regulate homeostasis and calcium signaling that have not been related to AD at the present time. Based on previous studies by our group and other laboratories, we propose the study of the importance of calcium regulation in the pathophysiology of AD by characterizing new genes, not previously related to AD, that play key role in Aß neurotoxicity and production.
The collaborators of this project are both national and international research groups.
The field of action is global.
This project is supported by the Spanish Ministry of Economy and Business through the grant Plan Estatal SAF2017-83372-R and FEDER funds/UE.
We consider that our findings could be used to propose new therapeutic targets for the treatment of AD, aimed at eliminating the intracellular alterations induced by Aß and these leading to its production, avoiding/reducing the aggregation and neurotoxicity of Aß.