Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Schizophrenia Linked to Defects in the Brain's Autophagy Pathway

By BiotechDaily International staff writers
Posted on 09 Jan 2014
Image: A functional magnetic resonance image (fMRI) showing brain areas more active in controls than in schizophrenia patients during a working memory task. Schizophrenia has been linked to decreased autophagy and enhanced cell death (Photo courtesy of Wikimedia Commons).
Image: A functional magnetic resonance image (fMRI) showing brain areas more active in controls than in schizophrenia patients during a working memory task. Schizophrenia has been linked to decreased autophagy and enhanced cell death (Photo courtesy of Wikimedia Commons).
A recent paper has linked schizophrenia to inhibition of the cellular degradative process autophagy in the hippocampus segment of the brain.

Autophagy is a self-degradative cellular process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Autophagy also plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria, endoplasmic reticulum, and peroxisomes, as well as eliminating intracellular pathogens. Thus, autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to nonapoptotic cell death. Autophagy can be either non-selective or selective in the removal of specific organelles, ribosomes, and protein aggregates, although the mechanisms regulating aspects of selective autophagy are not fully understood. Several key proteins govern the autophagy pathway including beclin1 and microtubule associated protein 1 light chain 3 (LC3).

Currently there are no objective tests for schizophrenia, and its diagnosis is based on an assortment of reported symptoms. In studying the causes of the syndrome investigators at Tel Aviv University (Israel) looked at factors linked to other brain disorders such as Alzheimer's disease, where death of brain cells has been linked to defects in the autophagy pathway.

The investigators analyzed postmortem brain samples from schizophrenia patients. They reported in the December 24, 2013, online edition of the journal Molecular Psychiatry that there was a brain-specific reduction in beclin1 expression in the hippocampus of schizophrenia patients, not detected in peripheral lymphocytes. This was in contrast to the proteins activity-dependent neuroprotective protein (ADNP) and ADNP2, which showed significantly increased expression in lymphocytes from related patients. The increase in ADNP was associated with the initial stages of the disease, and might possibly be a compensatory effect in response to the decline in beclin1.

At the protein level, ADNP was found to co-immunoprecipitate with LC3 suggesting a direct association with the autophagy process and paving the path to novel targets for drug design.

"We discovered a new pathway that plays a part in schizophrenia," said senior author Dr. Illana Gozes, professor of neurosciences at Tel Aviv University. "By identifying and targeting the proteins known to be involved in the pathway, we may be able to diagnose and treat the disease in new and more effective ways. It is all about balance. 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."

Related Links:
Tel Aviv University



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Disruption and removal of malaria parasites by the experimental drug (+)-SJ733 (Photo courtesy of the University of California, San Francisco).

Experimental Antimalaria Drug Induces the Immune System to Destroy Infected Red Blood Cells

An experimental drug for the treatment of malaria was found to induce morphological changes in infected erythrocytes that enabled the immune system to recognize and eliminate them. Investigators at... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.