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's Molecular 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
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.
discovered ADNP in 1999 and carved a protein fragment, NAP
, from it.
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's Sackler 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.
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.