Founded in 1963, Tel Aviv University is one of Israel's foremost research and teaching universities. Located in Israel's cultural, financial and industrial heartland, Tel Aviv University is at the forefront of basic and applied research in a wide variety
Now, Prof. Illana Gozes - the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, the director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine, and a member of the Sagol School of Neuroscience at Tel Aviv University - has discovered that an important cell-maintenance process called autophagy is reduced in the brains of schizophrenic patients.
The findings, published this week in Nature'sMolecular Psychiatry, advance the understanding of schizophrenia and could enable the development of new diagnostic tests and drug treatments for the disease.
"We discovered a new pathway that plays a part in schizophrenia," said Prof. Gozes.
Brain-cell death also occurs in schizophrenics, so Prof. Gozes and her colleagues set out to see if blocked autophagy could be involved in the progression of that condition as well.
They found RNA evidence of decreased levels of the protein beclin 1 in the hippocampus of schizophrenia patients, a brain region central to learning and memory.
Beclin 1 is central to initiating autophagy - its deficit suggests that the process is indeed blocked in schizophrenia patients.
The researchers say that developing drugs to boost beclin 1 levels and restart autophagy could offer a new way to treat schizophrenia.
"It is all about balance," said Prof Gozes.
"Paucity in beclin 1 may lead to decreased autophagy and enhanced cell death.
Our research suggests that normalizing beclin 1 levels in schizophrenia patients could restore balance and prevent harmful brain-cell death."
Next, the researchers looked at protein levels in the blood of schizophrenia patients.
They found no difference in beclin 1 levels, suggesting that the deficit is limited to the hippocampus.
This said, the researchers also found increased levels of another protein, activity-dependent neuroprotective protein (ADNP), discovered by Prof. Gozes and shown to be essential for brain formation and function, in the patients' white blood cells.
Prof. Gozes discovered ADNP in 1999 and carved a protein fragment, NAP, from it.
NAP mimics the protein nerve cell protecting properties.
In follow-up studies Prof. Gozes helped develop the drug candidate davunetide (NAP).
In Phase II clinical trials, davunetide (NAP) improved the ability of schizophrenic patients to cope with daily life.
A recent collaborative effort by Prof. Gozes and Dr. Sandra Cardoso and Dr. Raquel Esteves showed that NAP improved autophagy in cultures of brain-like cells.
Now Prof. Illana Gozes of Tel Aviv University'sSackler Faculty of Medicine has developed a new peptide in her lab, called NAP or Davunetide, which has the capacity to both protect and restore microtubule function.
The peptide is a compound derived from the protein ADNP, which regulates more than 400 genes and is essential for brain formation, memory, and behaviour.
Prof. Gozes and her team of researchers, including Dr. Yan Jouroukhin and graduate student Regin Ostritsky of TAU, observed that in animal models with microtubule damage, NAP was able to maintain or revive the transport of proteins and other materials in cells, ameliorating symptoms associated with neurodegeneration.
Prof. Gozes is the director of TAU's Adams Super Center for Brain Studies and holds the Lily and Avraham Gildor Chair for the Investigation of Growth Factors.
NAP appears to have widespread potential in terms of neuroprotection, says Prof. Gozes, who was recently awarded the Meitner-Humblodt Research Award for her lifelong contribution to the field of brain sciences.
"Abnormal tau proteins form tangles that contribute to the progression of Alzheimer's disease," said Illana Gozes, Ph.D., who led the research for the study.
"We showed here, for the first time, that the drug candidate NAP augmented microtubule movement in nerve cells.
At the molecular level, NAP, a fragment of activity-dependent neuroprotective protein (ADNP), enhanced tau-microtubule interactions that block the recruitment of tau to the tangles observed in Alzheimer's disease and related disorders."
Dr. Gozes is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, Head of the Elton Laboratory for Molecular Neuroendocrinology at TAU's Sackler Faculty of Medicine and a member of TAU's Adams Super Center for Brain Studies and the Sagol School of Neuroscience.She is responsible for discovering ADNP, a gene that is dysregulated in Alzheimer's.
Mutations in ADNP that occur in pregnancy are a major cause of autism with intellectual disability.
"ADNP and NAP operate through the stabilization of microtubules-tubes within the cell that maintain cellular shape," Dr. Gozes said.
Allon Therapeutics' proprietary information and technology are the products of more than a decade long research collaboration between Professor Illana Gozes of Tel Aviv University, Israel, and Dr. Douglas Brenneman formerly of the National Institutes of Health, US.
Professor Gozes and Dr. Brenneman then isolated the active components of the neuron-protecting, or neuroprotective, proteins.
Prior to founding Allon with Dr. Gozes in 2001, Dr. Spier was Chairman of the TSRI Society of Fellows, founder of the National Postdoctoral Association, a member of the Panel of Expert Scientists of Trends in Neuroscience, and serves on the Editorial Board of the Journal of Molecular Neuroscience, an active member of the American Association for the Advancement of Science, Neuroscience Section, and was a biotechnology consultant with the Technology Evaluation Group, LLC, since 1999.
Illana Gozes, Ph.D. - Chief Scientific OfficerDr. Gozes is a co-founder Allon Therapeutics and a Professor of Clinical Biochemistry, the Lily and Avraham Gildor Chair for the Investigation of Growth factors, Tel Aviv University (TAU), where she heads a research laboratory.Dr. Gozes awards and prizes include: the Bergmann Prize and the Neufeld award for outstanding (country-wise) BSF grants, the Juludan Prize, the Teva Founders Prize, Fogarty-Scholar-in-Residence (NIH) and the Israeli Society for Laboratory Studies for the best basic science work, 2001.She is co-inventor on more than 15 patents and patent applications, including the composition of matter patent on NAP, Allon's lead compound.
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