Research in mice sheds light on cellular pathways that underlie Alzheimers disease
A major international research effort has just revealed new insights into the cellular pathways that underlie the majority of Alzheimers disease (AD)-related diseases. Led by researchers at Imperial College London the study serves as a prelude to uncover new genes associated with the progression of Alzheimers disease.
The team focused their efforts on the interaction of two key processes in the brain that locomote cells along their path to the infarcts that cause AD pathology: phosphorylation (phosphorylation means the addition of hydrogen or the addition of an ion) and phosphorylation (phosphorylation means the removal of or addition of groups of a protein of the DNA or RNA genome) which occur simultaneously in the cells of the lesion allowing them to travel in discordance and cross-talk to the hippocampus – the part of the brain that is known to be affected in AD.
The paper published in the leading journal Nature Neuroscience provides the first comprehensive overview of the new research which has been led by Dr. Alexander Guerrero-Garca Professor of Molecular Neurodegeneration at Imperial. This is the first time that this scale-up effort has been undertaken by scientists from the following institutions across multiple continents.
For today a mouse model bearing a mouse replicase the essential enzyme of AD protection is used to identify disease components and assess how the disease progresses. By Ken M. Blagman former postdoctoral researcher at Imperial Space Research Institute and lead author it is shown that depolarisation (autophagy) the cellular button used by neurones to push themselves to the process of cell death is essential to keep synaptic connections alive. Small protein C so that it is blocked (called tyrosine kinase) prevents neuronal cells from dying which has a pivotal effect on survival in the pathology-prone brain. As such a paradigm for pathological dysautonomia has been discovered in mice and significant drugs are now available. This study was conducted at Imperials Centre for Neurodegenerative Diseases by postdoctoral fellows Professor Geoffrey Maynard (Clinical Medicine Research Unit Northumbria) Dr. Nathan Hughes (Medical Research CouncilWellcome Sanger Institute) Dr. Guillermo Champagne (Centre National de la Recherche ScientifiqueUniversit de Paris) Dr. Emmanuelle Bercoulan (Le Crdit de Paris) Professor Bret Eijkelkamp (Sageinst et de lUniversit de Paris) and Dr. Federico Pellecchia (ESCINSERMINSERMSainte Data).
In human blood samples from Alzheimers disease patients phosphorylation of small RNAs was found in high concentrations in the brain. These studies are the first steps toward the coming spring of 2019 when we hope that the results will that will convince decision-makers that this pre-clinical model is a powerful platform to screen for drug candidates that can intervene inside the brain of people living with AD emphasises Professor Devdutt Bhakshi Distinguished Professor at 1986 BC and a senior researcher at Imperial Clinical Research and Developmental Neurosurgery.
Chronic neural stress which is highly influenced by aging-related neurodegenerative diseases such as Alzheimers increases damage to blood-brain barrier components where their concentration remains lower. This can contribute to damage to the surrounding white matter (the way in which nerve cells communicate with each other) keeping the brain inactive for prolonged periods. This condition known as neuroinflammation is thought to involve multiple damaged tissue components (white matter) and central nervous system cells (neurons) exhibiting persistent activation in the brain. Current therapeutic strategies aimed at slowing down or stopping this dangerous progression are focused on blocking nerve barrier damage benign drugs such as cyclosilane or dimethylphenyltrinitrate (DMT) or pharmacological approaches.
Identifying new therapeutic targets might more likely be a long process before critical discoveries are made.