Israeli discovery could reverse Alzheimer’s damage

by David Shamah for Times of Israel:Research by a Tel Aviv University team may point the way to protecting cells from the damage wrought by Alzheimer’s disease, and even reverse damage that the disease caused before treatment. The method involves a protein similar to one which protects the brain from damage, but which is lacking in Alzheimer’s patients.What causes Alzheimer’s is still a mystery, but the direct physical conditions leading to the dementia associated with the disease are very clear to scientists. Plaque accumulations and tangles in neurons kill brain cells in Alzheimer’s sufferers, leading to the degeneration of cognitive function and the loss of memory associated with the disease.One of the most important objectives of Alzheimer’s research has been to figure out ways to protect brain cells from these senile plaques and neurofibrillary tangles. In a study published in the May edition of the Journal of Alzheimer's Disease, Tel Aviv University Prof. Illana Gozes describes how NAP, a snippet of a protein essential for brain formation, has been proven in previous studies to protect cognitive functioning. Loss of NAP exposes cells to physical damage that eventually destroys them, but applying proteins with NAP-like properties makes them healthy again.It’s just such a protein that Gozes and her team have discovered. The research, she said, could eventually lead to development of drugs to treat Alzheimer’s.Gozes holds the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and is director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine and a member of Tel Aviv University’s Sagol School of Neuroscience. “Several years ago we discovered that NAP showed efficacy in Phase 2 clinical trials in mild cognitive impairment patients, a precursor to Alzheimer’s,” she said. “Now, we’re investigating whether there are other novel NAP-like sequences in other proteins.”NAP, also known as davunetide, is an eight-amino acid peptide that has been shown to provide potent neuroprotection in several human trials. NAP is derived from activity-dependent neuroprotective protein (ADNP), a molecule that is essential for brain formation.“NAP operates through the stabilization of microtubules – tubes within the cell which maintain cellular shape. They serve as ‘train tracks’ for movement of biological material,” said Gozes. “In Alzheimer’s disease, these microtubules break down. The newly discovered protein fragments, just like NAP before them, work to protect microtubules, thereby protecting the cell.”In the study, Gozes and her team examined the tubulin (a subunit of the microtubule) and the protein TAU (tubulin-associated unit), important for assembly and maintenance of the microtubule. Abnormal TAU proteins form the tangles that contribute to Alzheimer’s. The larger the tangles, the more cognitive function is damaged.In tests on mice suffering from dementia-like characteristics which found the abnormal TAU proteins, a tubulin fragment with NAP-like sequences was applied to cells with very promising results, Gozes said. As NAP “evaporated,” the brain cells were less protected and deteriorated. The tubulin treatment reversed the damage. “We looked at the mouse ‘dementia’-afflicted brain and saw there was a reduction in the NAP parent protein, but upon treatment with the tubulin fragment, the protein was restored to normal levels,” she said. In addition, the treatment restored the size of mice brains, which had shrunk due to the disease.Further tests are set to be conducted on more animal cohorts. Eventually, an effective treatment for Alzheimer’s and other dementia-related diseases could come of this research, Gozes believes. “We clearly see here the protective effect of the treatment,” she said. “We witnessed the restorative and protective effects of totally new protein fragments, derived from proteins critical to cell function, in tissue cultures and on animal models.” Further work is needed, she said, but the team’s research could one day turn into a treatment to alleviate, or even reverse, Alzheimer’s disease.Source: http://bit.ly/1vturhD