Skip to main content

Blocking Transport Pathway to Prevent Development of Alzheimer's

Blocking a transport pathway through the brain cells offers new prospects to prevent the development of Alzheimer's. Wim Annaert and colleagues of VIB and K.U. Leuven discovered that two main agents involved in the inception of Alzheimer's disease, the amyloid beta precursor protein (APP) and the beta secretase enzyme (BACE1), follow a different path through the brain cells to meet up. It is during the eventual meeting between protein and enzyme that the basis is laid for the development of the disease.
The results of the study were published in the Proceedings of the National Academy of Sciences.

Wim Annaert suggests that "closing off or rerouting the path which beta secretase follows to get to APP may perhaps be used to inhibit the rise of the disease. However, a great deal of additional research will be necessary to confirm whether this discovery can effectively lead to a drug."


APP (red) and BACE1 (pink) follow distinct routes to the early endosome. Blocking specific points along the ARF6-mediated BACE internalization pathway has opposing effects on APP processing. ARF6-Q67L prevents formation of early endosomes and thus stunts A² production; ARF6-T27N stalls recycling of endosomes back to the cell surface, thereby increasing A² production. (Credit: Wim Annaert, copyright National Academy of Sciences).

Inhibiting the formation of amyloid plaques

The presence of amyloid plaques is typical of the brains of Alzheimer patients. These plaques are abnormal accumulations of a sticky short protein (beta amyloid) between the nerve cells. The beta amyloid peptide develops when the APP precursor protein is cut into pieces the wrong way, in a reaction which also involves the beta secretase enzyme. Overproduction of these peptides may give rise to the formation of plaques. The plaques disrupt the normal functioning of the brain. Preventing the formation of these plaques is a possible strategy for inhibiting the disease.

Alzheimer's disease

Alzheimer's is a memory disorder that affects up to 70% of patients with dementia. There are about 100 000 people with Alzheimer's in Belgium. The disease slowly -- step by step -- destroys brain cells in the deep part of the brain that serve for memory and knowledge. Since Alois Alzheimer first reported on the disease 100 years ago, scientists have been searching for ways of treating the disease.

R. Sannerud, I. Declerck, A. Peric, T. Raemaekers, G. Menendez, L. Zhou, B. Veerle, K. Coen, S. Munck, B. De Strooper, G. Schiavo, W. Annaert. PNAS Plus: ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1100745108

Source: VIB (the Flanders Institute for Biotechnology).
Labels:

Comments

Post a Comment

Popular posts from this blog

J147 Reverses Memory Deficits And Slows Alzheimer's In Mice

Source:  Salk Institute A drug developed by scientists at the Salk Institute for Biological Studies, known as J147, reverses memory deficits and slows Alzheimer's disease in aged mice following short-term treatment. The findings, published May 14 in the journal Alzheimer's Research and Therapy, may pave the way to a new treatment for Alzheimer's disease in humans.  "J147 is an exciting new compound because it really has strong potential to be an Alzheimer's disease therapeutic by slowing disease progression and reversing memory deficits following short-term treatment," says lead study author Marguerite Prior, a research associate in Salk's Cellular Neurobiology Laboratory. Despite years of research, there are no disease-modifying drugs for Alzheimer's. Current FDA-approved medications, including Aricept, Razadyne and Exelon, offer only fleeting short-term benefits for Alzheimer's patients, but they do nothing to slow the steady, irr
Post a Comment
Read more

Neuronal Switch to Prevent Neurodegenerative Diseases

Scientists at Northwestern University report a surprising discovery that offers a possible new route for the treatment of neurodegenerative diseases. In a study of the transparent roundworm C. elegans, they found that a genetic switch in master neurons inhibits the proper functioning of protective cell stress responses, leading to the accumulation of misfolded and damaged proteins. Neurodegenerative diseases, ranging from Huntington's and Parkinson's to amyotrophic lateral sclerosis and Alzheimer's, are believed to stem from early events that lead to an accumulation of damaged proteins in cells. Yet all animals, including humans, have an ancient and very powerful mechanism for detecting and responding to such damage, known as the heat shock response. "Why are these diseases so widespread if our cells have ways to detect and prevent damaged proteins from accumulating?" said Richard I. Morimoto, who led the research together with postdoctoral colleague Veena Prah
Post a Comment
Read more

Gene Expression in the Mouse Brain Provides Insights

A new atlas of gene expression in the mouse brain provides insight into how genes work in the outer part of the brain called the cerebral cortex. In humans, the cerebral cortex is the largest part of the brain, and the region responsible for memory, sensory perception and language. Mice and people share 90 percent of their genes so the atlas, which is based on the study of normal mice, lays a foundation for future studies of mouse models for human diseases and, eventually, the development of treatments. Researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and from Oxford University in the United Kingdom, published a description of the new atlas in the Aug. 25, 2011, journal Neuron. The study describes the activity of more than 11,000 genes in the six layers of brain cells that make up the cerebral cortex. "This study shows the power of genomic technologies for making unexpected discoveries about the basic biology of lif
Post a Comment
Read more