In a breakthrough, scientists have identified a potential cause of Alzheimer's based on a newly-discovered signalling pathway in cellular models of the disease.
Scientists so far have widely accepted that Alzheimer's disease is caused by the accumulation of a peptide called Amyloid beta.
When Amyloid beta is applied to neurons, neuronal morphology becomes abnormal and synaptic function is impaired. However, how Amyloid beta causes dysfunction is unknown.
The new study by researchers at the Max Planck Florida Institute for Neuroscience indicates that the presence of Amyloid beta triggers increased levels of a signalling protein, called centaurin-1 (CentA1), that appears to cause neuronal dysfunction - a potentially groundbreaking discovery that uncovers an important intermediary step in the progression of the disease.
"This study transforms our understanding of the direct cause of Alzheimer's disease. With further research, we may open up an entirely new avenue for treatments to combat this disease," said Principal Investigator Dr Ryohei Yasuda.
Scientists were able to identify CentA1 and measure its negative effects on neurons.
Utilising an RNA silencing technique, they turned down the cellular production of CentA1, and showed that affected neurons, exposed to Amyloid beta and exhibiting Alzheimer's related symptoms, returned to normal morphology and synaptic function, even with the continued presence of Amyloid beta.
They further found that increased CentA1 activates a series of proteins, and these proteins form a signalling pathway from CentA1 to neuronal dysfunction. Thus, inhibiting other proteins in the pathway also "cured" affected neurons.
The initial tests reported were conducted on rat brain slices. Ultimately, targeting the components of this newly identified signalling pathway has the potential to open the door for new pharmacological and gene therapies in treatment of Alzheimer's disease.
The research was published in The Journal of Neuroscience.
